An electro-absorption optical modulator based on dual-graphene-on-graphene configuration is presented and investigated. Four graphene layers are embedded in a silicon-on-insulator (SOI) waveguide, the total metal-graphene contact resistance of this structure is reduced 50% by the graphene layers co-electrode design. By optimizing the position of each graphene-on-graphene (GOG) layer in the waveguide, a strong interaction between graphene layers and light is obtained, which leads to a significant change of the effective mode index (EMI) in the waveguide. Calculations show that an electro-absorption optical modulator can achieve 34 dB extinction ratio (ER) and 100 GHz modulation bandwidth with 5 µm-long active region and 17.6 fJ/bit consumption.
The acute radiation-induced intestinal injury (RIII) has raised much concerns and is influenced by non-cytocidal radiation effects including the perturbations in gut microbiota. Although a number of studies have reported alteration in gut microbiota following radiation, little is known about its dynamic variation in the progression of acute RIII. In this study, mouse model were treated with total body irradiation (TBI) of 0, 4, 8 and 12 Gy, and the intestinal tissues and fecal samples were collected at 6 h, 3.5 d and 7 d post radiation. We found that the intestinal injuries were manifested in a radiation dose-dependent manner. Results from 16S rRNA gene sequencing demonstrated that the diversity of gut microbiota was not significantly affected at the prodromal stage of acute RIII, after 6 h of radiation. At the critical stage of acute RIII, after 3.5 d of radiation, the composition of gut microbiota was correlated with the radiation dose. The Pearson’s correlation analysis showed that the relative abundances of phylum Proteobacteria, genera Escherichia-Shigella and Eubacterium xylanophilum_group, and species Lactobacillus murinus exhibited linear correlations with radiation dose. At the recovery stage of acute RIII, after 7 d of radiation, the diversity of gut microbiota decreased as a whole, among which the relative abundance of phyla Proteobacteria and Bacteroides increased, while that of phylum Tenericutes and genus Roseburia decreased. The intra-gastric administration of compound probiotics for 14 days improved the survival duration of mice exposed to 9 Gy TBI, alleviated the intestinal epithelial injury and partially restored the diversity of gut microbiota. Our findings suggest that acute RIII is accompanied by the dysbiosis of gut microbiota, including its decreased diversity, reduced abundance of beneficial bacteria and increased abundance of pathogens. The gut microbiota cannot be used as sensitive biomarkers at the prodromal stage in acute RIII, but are potential biomarkers at the critical stage of acute RIII. The dysbiosis is persistent until the recovery stage of acute RIII, and interventions are needed to restore it. The administration of probiotics is an effective strategy to protect against acute RIII and subsequent dysbiosis.
The high radiosensitivity of the intestinal epithelium limits the outcomes of radiotherapy against abdominal malignancies, which results in poor prognosis. Currently, no effective prophylactic or therapeutic strategy is available to mitigate radiation toxicity in the intestine. Our previous study revealed that the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) attenuates radiation-induced intestinal injury (RIII). The aim of the present study was to determine the effect of EGCG on the intestinal flora of irradiated mice. EGCG administration reduced radiation-induced intestinal mucosal injury, and significantly increased the number of Lgr5+ intestinal stem cells (ISCs) and Ki67+ crypt cells. In addition, EGCG reversed radiation-induced gut dysbiosis, restored the Firmicutes/Bacteroidetes ratio, and increased the abundance of beneficial bacteria. Our findings provide novel insight into EGCG-mediated remission of RIII, revealing that EGCG could be a potential modulator of gut microbiota to prevent and treat RIII.
The gastrointestinal tract is a rapidly self-renewing system and is thus highly sensitive to ionizing radiation (IR). Unfortunately, methods for preventing and treating IR-induced gastrointestinal syndrome are limited. Volatile monoterpenoid perillaldehyde (PAH) is the major component of the essential oil extracted from perilla plants and has been demonstrated to have antioxidant, anti-inflammatory, antimicrobial activity, and antitumor effects. However, its role in preventing or alleviating radiation-induced injuries remains unknown. In this study, PAH prolonged the survival time and attenuated radiation-induced intestinal injury in whole abdominal lethally irradiated mice. PAH treatment also promoted the survival of crypt cells, attenuated radiation-induced DNA damage, and mitigated intestinal barrier damage in irradiated mice. The radioprotective effects of PAH in intestinal crypt organoids and human intestinal epithelial cell line (HIEC-6) were also identified. PAH-mediated radioprotection was associated with the upregulation of Nrf2, activation of the antioxidant pathway, and inhibition of ferroptosis. Notably, treatment with the Nrf2 inhibitor ML385 abolished the protective effects of PAH, indicating that Nrf2 activation is essential for PAH activity. The findings of this study collectively suggest that PAH is a promising therapeutic strategy for IR-induced intestinal injury.
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