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Graphical abstract, Oral mucositis is a common radiotherapy-induced complication among nasal, oral and laryngeal cancer (NOALC) patients. This complication leads to decreased quality of life and has few treatments. Here, fractionated radiation was performed to mimic radiotherapy for NOALCs in mouse models. Oral microbiota transplantation (OMT) mitigated oral mucositis, as judged by reconstructed epithelium and tongue papillae, fewer infiltrated leukocytes and more proliferative cells in the oral epithelium. The gut microbiota impacted oral mucositis progression, and OMT restructured oral and gut bacteria configurations and reprogrammed the gene expression profile of tongue tissues. In vivo silencing of glossal S100 calcium binding protein A9 debilitated the radioprotection of OMT. In light of clinical samples, we identified that patients with different alteration trends of Lactobacillaceae frequency presented different primary lesions and prognoses of NOALC following radiotherapy. Together, our findings provide new insights into the oral-gut microbiota axis and underpin the suggestion that OMT might be harnessed as a novel remedy to fight against oral mucositis in NOALC patients following radiotherapy in preclinical settings. Of note, oral microorganisms, such as Lactobacillaceae, might be employed as biomarkers to predict the prognosis of NOALC with radiotherapy.

Radioresistance is a major challenge in lung cancer radiotherapy (RT), and consequently, new radiosensitizers are urgently needed. MicroRNAs (miRNAs) have been demonstrated to participate in many important cellular processes including radiosensitization. MiR-365 is dysregulated in non-small cell lung cancer (NSCLC) and is able to restrain the development of NSCLC. However, the relationship between miR-365 and radiosensitivities of NSCLC cells remains largely unknown. Here we reveal that overexpression of miR-365 is able to enhance the radiosensitivity of NSCLC cells through targeting CDC25A. We found that the expression level of miR-365 was positively correlated with the radiosensitivity of NSCLC cell lines. Furthermore, our results showed that overexpression of miR-365 could sensitize A549 cells to the irradiation. However, knockdown of miR-365 in H460 cells could act the converse manner. Mechanically, miR-365 was able to directly target 3′UTR of cell division cycle 25A (CDC25A) mRNA and reduce the expression of CDC25A at the levels of mRNA and protein. And we confirmed that miR-365 could increase the radiosensitivity of NSCLC cells by targeting CDC25A using in vitro and in vivo assays. Taken together, restoration of miR-365 expression enhances the radiosensitivity of NSCLC cells by suppressing CDC25A, and miR-365 could be used as a radiosensitizer for NSCLC therapy.

Radiation therapy toward malignancies is often ineffective owing to radioresistance of cancer cells. On the basis of anti-tumor properties of cordycepin, we examined the effects of cordycepin on sensitizing breast cancer cells toward radiotherapy. Cordycepin administration promoted G2/M arrest and apoptosis of MCF-7 and MDA-MB-231 cells resulting in restraining the proliferation of the cells in vitro and in vivo following irradiation. Mechanistic investigations showed that the breast cancer cells cultured with cordycepin harbored higher levels of intracellular reactive oxygen species (ROS) and incremental numbers of γ-H2AX foci after irradiation exposure. Importantly, cordycepin treatment down-regulated the expression levels of Nuclear factor erythroid 2-related factor (Nrf2) and a series of downstream genes, such as heme oxygenase-1 (HO-1), to enhance ROS in breast cancer cells exposed to irradiation. Together, our observations demonstrate that cordycepin treatment sensitizes breast carcinoma cells toward irradiation via Nrf2/HO-1/ROS axis. Thus, our findings provide novel insights into the function and the underlying mechanism of cordycepin in radiotherapy, and suggest that cordycepin might be employed as a radiosensitizer during radiotherapy toward breast cancer in a pre-clinical setting.

Background: There remain unmet clinical needs for safe and effective regimen to fight against radiation injuries from medical irradiation or accidental exposure. Intestinal microbes play important roles in radiation damage. Diet is an efficacious mediator to educate the gut microbiota directly. Methods: In this case, we investigated whether 30% reduced calorie might ameliorate radiation enteritis and hematopoietic toxicity. Male and female C57BL/6J mice were either fed ad libitum (AL) or caloric restriction (CR) preconditioning for 10-day and then exposed to total body radiation (TBI) or total abdominal radiation (TAI). Findings: Gross examinations showed that short-term CR pretreatment restored hematogenic organs and improved intestinal architecture in both sexes of mice. Intriguingly, CR mitigated radiation-induced systemic and enteric inflammations in females, while the gut barrier function improved in irradiated male mice. 16S rRNA high-throughput sequencing was performed and showed that after 10-day of CR preconditioning, proinflammatory microbes including Helicobacter and Desulfovibrionaceae were lessened in female mice, while an enrichment of short-chain fatty acids (SCFAs)-producing bacteria such as Faecalibaculum, Clostridiales and Lactobacillus was observed in males. Gut flora shifts by fecal microbiota transplantation (FMT) or antibiotic administration counteracted CR-elicited radiation tolerance of both male and female mice, further demonstrated that the radioprotection of CR depends on the CR-restructured sex-specific gut microbiota configuration. Interpretation: Together, our findings provide new insights into CR in clinical applications, and indicate that short-term CR diet prior to radiation modulates the gut microbiota in a sex-dependent fashion, protecting male and female patients against the side effects caused by accidental or iatrogenic radiation challenge. Funding: Natural Science Foundation of China [81730086, 81872555, 82003399]; Science Foundation for Distinguished Young Scholars of Tianjin [20JCJQJC00100]; Drug Innovation Major Project of China [2018ZX09711001-007-008]. Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: The animal use protocol has been reviewed and approved by the Animal Ethical and Welfare Committee (AEWC)

Potential nuclear accidents propel serious environmental pollution, and the resultant radionuclide release devastates severely the environment severely and threatens aquatic organism survival. Likewise, ongoing climate change coupled with the gradual increase in global surface temperatures can also adversely impact the aquatic ecosystems. In the present study, we preconditioned zebrafish (Danio rerio) at three different temperatures (18 °C, 26 °C and 34 °C) to investigate the effects of a temperature profile on their radiosensitivity (exposure to 20 Gy of gamma rays) to identify the potential biochemical mechanism responsible for influencing radiosensitivity. We found that preconditioning of zebrafish at different temperatures moulded specific gut microbiota configurations and impacted hepatic glycometabolism and sensitivity to subsequent radiation. Following antibiotic treatment to reduce gut bacteria, these observed differences in the expression of hepatic glycometabolism-related genes and radiation-induced intestinal toxicity were minimal, supporting the hypothesis that the gut bacteria reshaped by different ambient temperatures might be the key modulators of hepatic functions and radiosensitivity in zebrafish. Together, our findings provide novel insights into the connection of radiation injuries with temperature alterations in fish, and suggest that maintaining the stability of gram-positive bacteria may be efficacious to protect aquatic organisms against short or long-term radioactive contamination in the context of global climate change.

Excessive alcohol consumption remains a major public health problem that affects millions of people worldwide. Accumulative experimental evidence has suggested an important involvement of gut microbiota in the modulation of host’s immunological and neurological functions. However, it is previously unknown whether enteric microbiota is implicated in the formation of alcohol withdrawal-induced anxiety. Using a murine model of chronic alcoholism and withdrawal, we examined the impact of alcohol consumption on the possible alterations of gut microbiota as well as alcohol withdrawal-induced anxiety and behavior changes. The 16S rRNA sequencing revealed that alcohol consumption did not alter the abundance of bacteria, but markedly changed the composition of gut microbiota. Moreover, the transplantation of enteric microbes from alcohol-fed mice to normal healthy controls remarkably shaped the composition of gut bacteria, and elicited behavioral signs of alcohol withdrawal-induced anxiety. Using quantitative real-time polymerase chain reaction, we further confirmed that the expression of genes implicated in alcohol addiction, BDNF, CRHR1 and OPRM1, was also altered by transplantation of gut microbes from alcohol-exposed donors. Collectively, our findings suggested a possibility that the alterations of gut microbiota composition might contribute to the development of alcohol withdrawal-induced anxiety, and reveal potentially new etiologies for treating alcohol addiction.

Humans benefit from nuclear technologies but consequently experience nuclear disasters or side effects of iatrogenic radiation. Hematopoietic system injury first arises upon radiation exposure. As an intricate new layer of genetic control, the posttranscriptional m6A modification of RNA has recently come under investigation and has been demonstrated to play pivotal roles in multiple physiological and pathological processes. However, how the m6A methylome functions in the hematopoietic system after irradiation remains ambiguous. Here, we uncovered the time-varying epitranscriptome-wide m6A methylome and transcriptome alterations in γ-ray-exposed mouse bone marrow. 4 Gy γ-irradiation rapidly (5 min and 2 h) and severely impaired the mouse hematopoietic system, including spleen and thymus weight, blood components, tissue inflammation and malondialdehyde (MDA) levels. The m6A content and expression of m6A related enzymes were altered. Gamma-irradiation triggered dynamic and reversible m6A modification profiles and altered mRNA expression, where both m6A fold-enrichment and mRNA expression most followed the (5 min_up/2 h_down) pattern. The CDS enrichment region preferentially upregulated m6A peaks at 5 min. Moreover, the main GO and KEGG pathways were closely related to metabolism and the classical radiation response. Finally, m6A modifications correlated with transcriptional regulation of genes in multiple aspects. Blocking the expression of m6A demethylases FTO and ALKBH5 mitigated radiation hematopoietic toxicity. Together, our findings present the comprehensive landscape of mRNA m6A methylation in the mouse hematopoietic system in response to γ-irradiation, shedding light on the significance of m6A modifications in mammalian radiobiology. Regulation of the epitranscriptome may be exploited as a strategy against radiation damage.

Radiotherapy is often employed to treat abdominal and pelvic malignancies, but is frequently accompanied by diverse acute and chronic local injuries. It was previously unknown whether abdominal and pelvic radiotherapy impairs distant cognitive dysfunction. In the present study, we demonstrated that total abdominal irradiation (TAI) exposure caused cognitive deficits in mouse models. Mechanically, microarray assay analysis revealed that TAI elevated the expression level of miR-34a-5p in small intestine tissues and peripheral blood (PD), which targeted the 3′UTR of Brain-derived neurotrophic factor ( Bdnf ) mRNA in hippocampus to mediate cognitive dysfunction. Tail intravenous injection of miR-34a-5p antagomir immediately after TAI exposure rescued TAI-mediated cognitive impairment via blocking the up-regulation of miR-34a-5p in PD, resulting in restoring the Bdnf expression in the hippocampus. More importantly, high throughput sequencing validated that the gut bacterial composition of mice was shifted after TAI exposure, which was retained by miR-34a-5p antagomir injection. Thus, our findings provide new insights into pathogenic mechanism underlying abdominal and pelvic radiotherapy-mediated distant cognitive impairment.

An ideal way to have the best of both worlds for environmental protection and energy conservation should be to juggle photocatalytic degrading pollutants and producing hydrogen from the pollutant solution synchronously. Herein, we have designed and synthesized a new 3D flower-like p-n-p heterostructure β-Ni(OH)2/NiS/TiO2 as a photocatalytic device, which is ideally suited for both removal of anionic dye methyl orange (MO), and release of hydrogen from the MO solution driven by photoelectric conversion without the need for using noble metals. The formation structure with optimal molar ratio 0.01-β-Ni(OH)2/0.001-NiS/TiO2 shows superior photocatalytic activity for removal of anionic dye MO and releasing hydrogen, its removal efficiency can reach as high as 98% in 15 min and the production of hydrogen is about 7.2 μmolh−1 from the MO solution. Results and analyses show that the outstanding performances of the sample should be attributed to the synergistic effects on two aspects. One is the high efficient charge separation and transfer driven by the internal electric field at the interfaces of NiS/TiO2 and the exposed high energy {001} facets of TiO2. The other is the modifier β-Ni(OH)2 as an assistant sacrificial agent can play an important role of the holes transfer for charge carriers transport balance in the oxidation-reduction process, and the generated active species NiOOH also has a beneficial effect on degrading MO and releasing hydrogen.

We have reported that hematopoietic system injury induced by total body irradiation (TBI) leads to generation of intracellular reactive oxygen species (ROS) and DNA damage, which are ameliorated by antioxidant agents. In the present study, we reported that administration of DIM, a potent antioxidant agent, not only protected mice against TBI-induced lethality, also ameliorated TBI-induced hematopoietic injury. The latter effect was probably attributable to DIM's inhibition of TBI-induced increases in ROS production in hematopoietic stem cells (HSCs) and the phosphorylation of histone H2AX (γ-H2AX). In particular, DIM led to significant improvements in bone marrow (BM) HSC frequency, hematopoietic progenitor cell (HPC) clonogenic function, and multilineage engraftment after transplantation. A downregulation of NADPH oxidase 4 (NOX4) and an upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression were observed following DIM treatment. Notably, the anti-apoptotic potential of DIM was correlated with increased expression of the anti-apoptotic protein Bcl-2 and decreased expression of the pro-apoptotic protein Bax. These findings suggest that DIM attenuates TBI-induced hematopoietic injury through the inhibition of both oxidative stress in HSCs and hematopoietic cell apoptosis. Furthermore, we demonstrated that DIM protected BM hematopoietic cells against ionizing radiation and led to increased clonogenicity in vitro. Therefore, DIM has the potential to be used as an effective radioprotectant to ameliorate TBI-induced hematopoietic injury.

Certified reference materials (CRMs) with high accuracy and traceability are essential tools for validation of analytical methods and calibration of equipment. They are widely used in various fields and have an important role in analytical science. In this study, tangeretin purity certified reference material was first developed in compliance with the principles of ISO guides. The investigation included preparation, characterization, homogeneity test, stability study and uncertainty estimation. In the characterization, mass balance method (MB) and differential scanning calorimetry (DSC) were simultaneously utilized, which would make up for the deficiency of a single method and cross-check the determination results. The mass balance method involved measurement of main component, as well as moisture, volatile impurities and inorganic impurities. Homogeneity, together with short-term and long-term stability, was investigated and the uncertainty estimation was performed. The results showed that tangeretin CRM was sufficiently homogeneous and stable for 12 months at 4 °C. The certified value is 99.8%, and the expanded uncertainty is 0.1% (k = 2).

Nuclear pollution intertwined accidental irradiation not only triggers acute and chronic radiation syndromes, but also endangers embryonic development in sight of uncontrollable gene mutation. Metformin (MET), a classic hypoglycemic drug, has been identified to possess multiple properties. In this study, we explored the radioprotective effects of MET on the developmental abnormalities and deformities induced by irradiation among three “star drugs”. Specifically, zebrafish (Danio rerio) embryos exposed to 5.2 Gy gamma irradiation at 4 h post fertilization (hpf) showed overt developmental toxicity, including hatching delay, hatching rate decrease, developmental indexes reduction, morphological abnormalities occurrence and motor ability decline. However, MET treatment erased the radiation-induced phenotypes. In addition, MET degraded inflammatory reaction, hinders apoptosis response, and reprograms the development-related genes expression, such as sox2, sox3, sox19a and p53, in zebrafish embryos following radiation challenge. Together, our findings provide novel insights into metformin, and underpin that metformin might be employed as a promising radioprotector for radiation-induced early developmental toxicity in pre-clinical settings.

Plasma electrolytic oxidation of Zircaloy-2 at constant rms current is examined in silicate and aluminate electrolytes, revealing significantly different behaviors in the growth kinetics and properties of the coatings. Coatings thicken continuously in the silicate electrolyte, while in the aluminate electrolyte, the thickness reaches a relatively constant value. The latter coincides with changing appearances of discharges and detachment of an outer coating layer. Dissolution of zirconium is faster in the silicate electrolyte in the early stage of PEO, but is faster in the aluminate electrolyte following coating breakdown. The pre-spallation coating formed in the aluminate electrolyte shows superior wear resistance, which can be ascribed to its relative compactness, associated with the presence of tetragonal zirconia stabilized by aluminium species.