Repeated radon exposure induced ATM kinase-mediated DNA damage response and protective autophagy in mice and human bronchial epithelial cells.

OBJECTIVE: Radon ( 222 Rn) is a naturally occurring radioactive gas that has been closely linked with the development of lung cancer. In this study, we investigated the radon-induced DNA strand breaks, a critical event in lung carcinogenesis, and the corresponding DNA damage response (DDR) in mice and human bronchial epithelial (BEAS-2B) cells. METHODS: Biomarkers of DNA double-strand breaks (DSBs), DNA repair response to DSBs, ataxia-telangiectasia mutated (ATM) kinase, autophagy, and a cell apoptosis signaling pathway as well as cell-cycle arrest and the rate of apoptosis were determined in mouse lung and BEAS-2B cells after radon exposure. RESULTS: Repeated radon exposure induced DSBs indicated by the increasing expressions of γ-Histone 2AX (H2AX) protein and H2AX gene in a time and dose-dependent manner. Additionally, a panel of ATM-dependent repair cascades [i.e. non-homologous DNA end joining (NHEJ), cell-cycle arrest and the p38 mitogen activated protein kinase (p38MAPK)/Bax apoptosis signaling pathway] as well as the autophagy process were activated. Inhibition of autophagy by 3-methyladenine pre-treatment partially reversed the expression of NHEJ-related genes induced by radon exposure in BEAS-2B cells. CONCLUSIONS: The findings demonstrated that long-term exposure to radon gas induced DNA lesions in the form of DSBs and a series of ATM-dependent DDR pathways. Activation of the ATM-mediated autophagy may provide a protective and pro-survival effect on radon-induced DSBs.

1,25(OH)2D3 inhibits pancreatic stellate cells activation and promotes insulin secretion in T2DM.

PURPOSE: To evaluate the effect and mechanism of 1,25(OH)2D3 on pancreatic stellate cells (PSCs) in type 2 diabetes mellitus (T2DM). METHODS: A mouse model of T2DM was successfully established by high-fat diet (HFD) /streptozotocin (STZ) and administered 1,25(OH)2D3 for 3 weeks. Fasting blood glucose (FBG), glycated hemoglobin A1c (GHbA1c), insulin (INS) and glucose tolerance were measured. Histopathology changes and fibrosis of pancreas were examined by hematoxylin and eosin staining and Masson staining. Mouse PSCs were extracted, co-cultured with mouse insulinoma ß cells (MIN6 cells) and treated with 1,25(OH)2D3. ELISA detection of inflammatory factor expression. Tissue reactive oxygen species (ROS) levels were also measured. Immunofluorescence or Western blotting were used to measure fibrosis and inflammation-related protein expression. RESULTS: PSCs activation and islets fibrosis in T2DM mice. Elevated blood glucose was accompanied by significant increases in serum inflammatory cytokines and tissue ROS levels. 1,25(OH)2D3 attenuated islet fibrosis by reducing hyperglycemia, ROS levels, and inflammatory factors expression. Additionally, the co-culture system confirmed that 1,25(OH)2D3 inhibited PSCs activation, reduced the secretion of pro-inflammatory cytokines, down-regulated the expression of fibrosis and inflammation-related proteins, and promoted insulin secretion. CONCLUSION: Our findings identify that PSCs activation contributes to islet fibrosis and ß-cell dysfunction. 1,25(OH)2D3 exerts beneficial effects on T2DM potentially by inhibiting PSCs activation and inflammatory response, highlighting promising control strategies of T2DM by vitamin D.

PM2.5 induce neurotoxicity via iron overload and redox imbalance mediated-ferroptosis in HT22 cells.

PM2.5 is an important risk factor for the development and progression of cognitive impairment-related diseases. Ferroptosis, a new form of cell death driven by iron overload and lipid peroxidation, is proposed to have significant implications. To verify the possible role of ferroptosis in PM2.5-induced neurotoxicity, we investigated the cytotoxicity, intracellular iron content, iron metabolism-related genes, oxidative stress indices and indicators involving in Nrf2 and ferroptosis signaling pathways. Neurotoxicity biomarkers as well as the ferroptotic cell morphological changes were determined by Western Blot and TEM analysis. Our results revealed that PM2.5 induced cytotoxicity, lipid peroxidation, as indicated by MDA content, and neurotoxicity via Aß deposition in a dose-related manner. Decreased cell viability and excessive iron accumulation in HT-22 cells can be partially blocked by ferroptosis inhibitors. Interestingly, GPX activity, Nrf2, and its regulated ferroptotic-related proteins (i.e. GPX4 and HO-1) were significantly up-regulated by PM2.5. Moreover, gene expression of DMT1, TfR1, IRP2 and FPN1 involved in iron homeostasis and NCOA4-dependent ferritinophagy were activated after PM2.5 exposure. The results demonstrated that PM2.5 triggered ferritinophagy-dependent ferroptotic cell death due to iron overload and redox imbalance. Activation of Nrf2 signaling pathways may confer a protective mechanism for PM2.5-induced oxidative stress and ferroptosis.

Hepatotoxicity induced in rats by chronic exposure to F-53B, an emerging replacement of perfluorooctane sulfonate (PFOS).

A plethora of studies have shown the prominent hepatotoxicity caused by perfluorooctane sulfonate (PFOS), yet the research on the causality of F-53 B (an alternative for PFOS) exposure and liver toxicity, especially in mammals, is largely limited. To investigate the effects that chronic exposure to F-53 B exert on livers, in the present study, male SD rats were administrated with F-53 B in a certain dose range (0, 1, 10, 100, 1000 µg/L, eight rats per group) for 6 months via drinking water and the hepatotoxicity resulted in was explored. We reported that chronic exposure to 100 and 1000 µg/L F-53 B induced remarkable histopathological changes in liver tissues such as distinct swollen cells and portal vein congestion. In addition, the increase of cytokines IL-6, IL-2, and IL-8 upon long-term administration of F-53 B demonstrated the high level of inflammation. Moreover, F-53 B exposure was revealed to disrupt the lipid metabolism in the rat livers, mainly manifesting as the upregulation of some proteins involved in lipid synthesis and degradation, including ACC, FASN, SREBP-1c as well as ACOX1. These findings provided new evidence for the adverse effects caused by chronic exposure to F-53 B in rodents. It is crucial for industries, regulatory agencies as well as the public to remain vigilant about the adverse health effects associated with the emerging PFOS substitutes such as F-53 B. Implementation of regular monitoring and risk assessments is of great importance to alleviate environmental concerns towards PFOS alternatives exposure, and furthermore, to minimize the latent health risks to the public health.

Repeated radon exposure induced epithelial-mesenchymal transition-like transformation via disruption of p53-dependent mitochondrial function.

Backgrouds: As a human carcinogen, radon and its progeny are the second most important risk factor for lung cancer after smoking. The tumor suppressor gene, p53, is reported to play an important role in the maintenance of mitochondrial function. In this work, we investigated the association between p53 and p53-responsive signaling pathways and radon-induced carcinogenesis. Methods: After repeated radon exposure, the malignant characteristics, cell cycle arrest, cell apoptotic rate, adenosine triphosphate (ATP) content, reactive oxygen species (ROS) level, mitochondrial DNA (mtDNA) copy number as well as indicative biomarkers involved in mitochondrial energy metabolism were evaluated in BEAS-2B cells or BALB-c mouse lung tissue. Results: Radon exposure induced epithelial-mesenchymal transition (EMT)-like transformation in BEAS-2B cells, as indicated by increased cell proliferation and migration. Additional mitochondrial alterations, including decreased ATP content, increased ROS levels, mtDNA copy numbers, cell apoptosis, and G2/M cell cycle arrest were observed. Radon exposure caused an energy generation shift from aerobic respiration to glycolysis as reflected by increased expression of TIGAR and p53R2 proteins and decreased expression of SCO2 protein in BEAS-2B cells, and increased expression of p53, SCO2 and TIGAR proteins in mouse lung tissue, respectively. The effects of p53 deficiency on the prevention of mitochondrial dysfunction suggested a protective role of p53 in radon-induced malignant-like features in BEAS-2B cells. Conclusions: Repeated radon exposure induced EMT-like transformation in BEAS-2B cells via disruption of mitochondrial function. Activation of p53 and p53-responsive signaling pathways in BEAS-2B cells and BALB-c mice may confer a protective mechanism for radon-induced lung injury.

Dialogic Priming and Dynamic Resonance in Autism: Creativity Competing with Engagement in Chinese Children with ASD.

A growing body of research has focused on the relationship between priming and engagement through dialogue (e.g. Tantucci and Wang in Appl Linguist 43(1):115-146, 2022; Mikulincer et al. in Cognit Emotion 25:519-531, 2011). The present study addresses this issue also in relation to creativity and provides a new applied model to measure intersubjective engagement in ASD vs neurotypical populations' speech. We compared two balanced corpora of naturalistic Mandarin interaction of typically developing children and children diagnosed with ASD (cf. Zhou and Zhang in Xueqian jiaoyu yanjiu [Stud Preschool Educ] 6:72-84, 2020). We fitted a mixed effects linear regression showing that, in both neurotypical and ASD populations, dialogic priming significantly correlates with engagement and with whether the child could creatively re-use the original input to produce a new construction. What we found is that creativity and intersubjective engagement are in competition in children with ASD in contrast with the neurotypical population. This finding points to a relatively impeded ability in ASD to re-combine creatively a priming input during the here-and-now of a dialogic event.

Matrix Regeneration Ability In Situ Induced by a Silk Fibroin Small-Caliber Artificial Blood Vessel In Vivo.

The success of a small-caliber artificial vascular graft in the host in order to obtain functional tissue regeneration and remodeling remains a great challenge in clinical application. In our previous work, a silk-based, small-caliber tubular scaffold (SFTS) showed excellent mechanical properties, long-term patency and rapid endothelialization capabilities. On this basis, the aim of the present study was to evaluate the vascular reconstruction process after implantation to replace the common carotid artery in rabbits. The new tissue on both sides of the SFTSs at 1 month was clearly observed. Inside the SFTSs, the extracellular matrix (ECM) was deposited on the pore wall at 1 month and continued to increase during the follow-up period. The self-assembled collagen fibers and elastic fibers were clearly visible in a circumferential arrangement at 6 months and were similar to autologous blood vessels. The positive expression rate of Lysyl oxidase-1 (LOXL-1) was positively correlated with the formation and maturity of collagen fibers and elastic fibers. In summary, the findings of the tissue regeneration processes indicated that the bionic SFTSs induced in situ angiogenesis in defects.

Melatonin protects against nonylphenol caused pancreatic ß-cells damage through MDM2-P53-P21 axis.

Nonylphenol (NP) is an endocrine disrupting chemical, which widely exists in environment and can result in multiple system dysfunction. Pancreas as one of the most important organs is sensitive to NP, while the detail toxic effect is still less studied. Previously, we unveiled nonylphenol causes pancreatic damage in rats, herein, we further explore the potential mechanism and seek protection strategy in vitro. Insulinoma (INS-1) cells exposed to NP were observed to suffer oxidative stress and mitochondrial dysfunction, as reflected by the abnormal levels of reactive oxygen species, malonic dialdehyde, superoxide dismutase, Ca2+, and mitochondrial membrane potential. Melatonin (MT) was found to alleviate NP-induced mitochondrial dysfunction and oxidative stress, further inhibit apoptosis and restore pancreas function. Mechanically, MT induced the MDM2-P53-P21 signaling, which upregulated the Nrf2 signaling pathway. In summary, our study clarified NP-induced INS-1 cells mitochondrial dysfunction and oxidative stress, which could be ameliorated by MT through MDM2-P53-P21 axis.

The mediating effect of psychological capital on the relationship between psychological stress and distress among chinese nursing students: a cross-sectional study.

BACKGROUND: With the COVID-19 outbreak in China, the Chinese government took measures to prevent and control the spread of the virus. In-person teaching was replaced by distance learning, which was an unknown challenge for students. In this context, little is known about the perceived distress of nursing students and the relationship between psychological capital, perceived distress, and psychological stress. This study examined the relationship between psychological capital, psychological distress, and perceived stress, and the mediating role of psychological capital in the relationship between perceived stress and psychological distress among nursing students. METHODS: This cross-sectional survey was conducted between January and December 2020 using a convenience sampling method involving 359 undergraduate and specialist nursing students at a tertiary hospital in Shandong Province. Standardised instruments were used to measure psychological capital, psychological stress, and perceived stress. We used SPSS 24.0 and PROCESS macro to analyse the data. RESULTS: There was a statistically significant difference in perceived stress among students based on whether they liked the nursing profession (P < 0.01). Relative to nursing college students, undergraduates experienced significantly higher levels of perceived stress (P < 0.01). Nevertheless, there were no significant differences in perceived stress according to gender, place of residence, and being an only child. Psychological distress was positively correlated (r = 0.632, p < 0.001) with perceived stress (r =-0.662, p < 0.001), whereas it was negatively correlated with psychological capital. Psychological capital played a potential mediating role in the relationship between psychological distress and perceived stress. CONCLUSIONS: Psychological distress was negatively correlated with psychological capital, and positively correlated with perceived stress. Mediation analyses indicated that psychological capital partially mediated the relationship between perceived stress and psychological distress. Educators should therefore heed students' perceived stress and develop appropriate mental health counselling programmes for students in the curriculum that could help them reduce their psychological distress. In clinical practice, nursing managers must take effective measures, such as skills training, to improve the psychological capital of nursing students and reduce the negative impact of their psychological distress.

Genome-wide identification, evolutionary and expression analyses of LEA gene family in peanut (Arachis hypogaea L.).

BACKGROUND: Late embryogenesis abundant (LEA) proteins are a group of highly hydrophilic glycine-rich proteins, which accumulate in the late stage of seed maturation and are associated with many abiotic stresses. However, few peanut LEA genes had been reported, and the research on the number, location, structure, molecular phylogeny and expression of AhLEAs was very limited. RESULTS: In this study, 126 LEA genes were identified in the peanut genome through genome-wide analysis and were further divided into eight groups. Sequence analysis showed that most of the AhLEAs (85.7%) had no or only one intron. LEA genes were randomly distributed on 20 chromosomes. Compared with tandem duplication, segmental duplication played a more critical role in AhLEAs amplication, and 93 segmental duplication AhLEAs and 5 pairs of tandem duplication genes were identified. Synteny analysis showed that some AhLEAs genes come from a common ancestor, and genome rearrangement and translocation occurred among these genomes. Almost all promoters of LEAs contain ABRE, MYB recognition sites, MYC recognition sites, and ERE cis-acting elements, suggesting that the LEA genes were involved in stress response. Gene transcription analyses revealed that most of the LEAs were expressed in the late stages of peanut embryonic development. LEA3 (AH16G06810.1, AH06G03960.1), and Dehydrin (AH07G18700.1, AH17G19710.1) were highly expressed in roots, stems, leaves and flowers. Moreover, 100 AhLEAs were involved in response to drought, low-temperature, or Al stresses. Some LEAs that were regulated by different abiotic stresses were also regulated by hormones including ABA, brassinolide, ethylene and salicylic acid. Interestingly, AhLEAs that were up-regulated by ethylene and salicylic acid showed obvious subfamily preferences. Furthermore, three AhLEA genes, AhLEA1, AhLEA3-1, and AhLEA3-3, which were up-regulated by drought, low-temperature, or Al stresses was proved to enhance cold and Al tolerance in yeast, and AhLEA3-1 enhanced the drought tolerance in yeast. CONCLUSIONS: AhLEAs are involved in abiotic stress response, and segmental duplication plays an important role in the evolution and amplification of AhLEAs. The genome-wide identification, classification, evolutionary and transcription analyses of the AhLEA gene family provide a foundation for further exploring the LEA genes' function in response to abiotic stress in peanuts.

A new approach for reducing pollutants level: a longitudinal cohort study of physical exercises in young people.

BACKGROUND: The present study aimed to evaluate the elimination of three common pollutants (dimethoate, benzo(a)pyrene (BaP) and bisphenol A (BPA) by different physical exercises and to assess the possible factors which could affect the pollutants elimination. METHODS: A total of 200 individuals who chose different kinds of exercises in accordance to their own wish were recruited. The levels of urinary pollutants were measured using ß-glucuronidase hydrolysis followed by a high-performance liquid chromatography tandem mass spectrometry-based method. RESULTS: Totally, the levels of dimethoate, BaP and BPA were reduced after physical exercises. However, the elimination of BaP in male was higher than that in female but the elimination of BPA in female was higher than that in male. Multivariate logistic regression showed that the degree of heart rate (HR) change was a protective factor affecting the improvement effect of dimethoate, BaP and BPA while BMI (body mass index) was a risk factor. Nevertheless, sex was a risk factor affecting the improvement of dimethoate and BaP but had a lower efficacy on BPA improvement. CONCLUSION: The present findings indicate that physical exercises can be considered as a novel approach to eliminate pollutants level in human body and can also give suggestions for choosing specific physical exercises to male and female individuals. Moreover, those who are with higher BMI need to lose weight before eliminating pollutant level through physical exercises.

Acetylene/Vinylene-Bridged π-Conjugated Covalent Triazine Polymers for Photocatalytic Aerobic Oxidation Reactions under Visible Light Irradiation.

Solar-driven photocatalytic chemical transformation provides a sustainable strategy to produce valuable feedstock, but designing photocatalysts with high efficiency remains challenging. Herein, two acetylene- or vinylene-bridged π-conjugated covalent triazine polymers, A-CTP-DPA and V-CTP-DPE, were successfully fabricated toward metal-free photocatalytic oxidation under visible light irradiation. Compared to the one without acetylene or vinylene bridge, both resulting polymers exhibited superior activity in photocatalytic selective oxidation of sulfides and oxidative coupling of amines; in particular, A-CTP-DPA delivered an optimal photocatalytic performance. The superior activity was attributed to the broadened spectral response range, effective separation, rapid transportation of photogenerated charge carriers, and abundant active sites for photogenerated electrons due to the existence of the acetylene bridge in the framework. This work highlights the potential of acetylene and vinylene bridges in tuning catalytic efficiency of organic semiconductors, providing a guideline for the design of efficient photocatalysts.

Urinary levels of dimethoate, bisphenol A and benzo[a]pyrene in first-year students of Hohai University from different geographical regions.

BACKGROUND: The objective of this study was to detect the urinary levels of dimethoate, benzo(a) pyrene (BaP), and bisphenol A (BPA) in first-year Hohai University students with different geographic origins. METHODS: First-morning urine samples were collected from 540 healthy freshmen aged 17 to 19 years. Chemical levels were measured using ß-glucuronidase hydrolysis followed by a high-performance liquid chromatography-tandem mass spectrometry-based method. Geometric means (GMs) of these three chemicals are presented by body mass index (BMI) and location in a volume-based and creatinine-standardized way. RESULTS: GM concentrations of omethoate, BPA and 3-OHBaP were 9.47 µg/L (10.80 µg/g creatinine), 3.54 µg/L (4.04 µg/g creatinine) and 0.34 ng/L (0.39 ng/g creatinine), respectively. The GM concentration of omethoate in males was significantly higher than that in females. The individuals with a BMI higher than 23.9 had higher GM concentrations of omethoate, BPA, and 3-OHBaP. The inhabitants of Southwest China had significantly lower GM concentrations of omethoate, BPA, and 3-OHBaP than those who lived in other locations in China. CONCLUSION: The average level of environmental chemical accumulation in freshmen is lower in Southwest China and differs in youth who live in different regions. In addition, obesity is correlated with higher toxin levels in youth.

Incremental predictive value of left atrial strain and left atrial appendage function in rhythm outcome of non-valvular atrial fibrillation patients after catheter ablation.

OBJECTIVE: The purpose of this study was to develop a non-invasive and convenient nomogram based on speckle tracking echocardiography, left atrial appendage function and clinical factors to predict the risk of atrial fibrillation (AF) recurrence after catheter ablation. METHODS: A total of 124 prospectively consecutive patients with AF treated with catheter ablation in our hospital was retrospectively analysis. Baseline echocardiographic parameters were measured by using transthoracic and transesophageal echocardiography before ablation. Multivariate analysis was performed for selecting predictors for a nomogram and internal validation and calibration were evaluated by the bootstep method. RESULTS: During the follow-up of 12±3 months, 41 patients (33.1%) occurred AF recurrence after catheter ablation, while 83 patients (66.9%) had maintained sinus rhythm. Four predictors (AF type, left atrial appendage emptying flow velocity, left Atrial maximal volumes index and global longitudinal strain) with the P<0.5 was selected into the nomogram according to multivariate findings. Internal validation by bootstrapping with 1000 resamples was determined C-index of the nomogram for prediction AF recurrence was 0.901, which showed optimal discrimination and calibration of the established nomogram. CONCLUSIONS: Nomogram based on echocardiography and clinical characteristics had good predictive performance for the possibility of AF recurrence, which providing practical guidance for individualised management of patients with AF after catheter ablation.

Protection of melatonin against long-term radon exposure-caused lung injury.

Radon is one of the major pathogenic factors worldwide. Recently, epidemiological studies have suggested that radon exposure plays an important role in lung injury, which could further cause cancer. However, the toxic effects and underlying mechanism on lung injury are still not clear. Here, we identified the detailed toxic effects of long-term radon exposure. Specifically, the manifestations were inflammatory response and cell apoptosis in dose- and time-dependent manners. In detail, it caused the mitochondrial dysfunction and oxidative stress as determined by the abnormal levels of mitochondrial DNA copy number, adenosine triphosphate, mitochondrial membrane potential, superoxide dismutase, and cycloxygenase-2. Furthermore, we found that melatonin treatment ameliorated mitochondrial dysfunction and attenuated the levels of oxidative stress caused by long-term radon exposure, which could further inhibit the lung tissue apoptosis as determined by the decreased levels of cleaved caspase 3. Our study would provide potential therapeutic application of melatonin on lung tissue injury caused by long-term radon exposure.

Motility and function of smooth muscle cells in a silk small-caliber tubular scaffold after replacement of rabbit common carotid artery.

Cell infiltration and proliferation are prerequisites for tissue regeneration and repair. The aim of the present study was to evaluate the motility and function of vascular smooth muscle cells (SMCs) in a silk-based small-caliber artificial blood vessel (SFTS) following implantation to replace the common carotid artery in rabbits. Hematoxylin and eosin (HE) staining showed a number of SMCs clearly distributed in the scaffold at 1 month, which gradually increased up to 80-90% of autologous blood vessels at 3 months and was 100% at 12 months. Smooth muscle myosin heavy chain (SM-MHC) and α-smooth muscle actin (α-SMA) are specific markers of SMCs. Real-time PCR results showed that the gene expression level of α-SMA in SFTSs was significantly down-regulated within 6 months, except in the early stage of implantation. The relative expression level of α-SMA at 12 months was five times higher than that at 3 months, indicating that SMCs phenotype transformed from synthetic to contractile. The SM-MHC+ and α-SMA+ SMCs were disorderly distributed in the scaffolds at 1 month, but became ordered along the circumference 6 months after grafting as shown by immunohistochemistry. Results indicated that the bionic SFTSs were able to induce in situ angiogenesis in defects.

1α,25(OH)2D3 Radiosensitizes Cancer Cells by Activating the NADPH/ROS Pathway.

The radioresistance of tumors affect the outcome of radiotherapy. Accumulating data suggest that 1α,25(OH)2D3 is a potential anti-oncogenic molecule in various cancers. In the present study, we investigated the radiosensitive effects and underlying mechanisms of 1α,25(OH)2D3 in vitro and in vivo. We found that 1α,25(OH)2D3 enhanced the radiosensitivity of lung cancer and ovarian cancer cells by promoting the NADPH oxidase-ROS-apoptosis axis. Compared to the group that only received radiation, the survival fraction and self-renewal capacity of cancer cells treated with a combination of 1α,25(OH)2D3 and radiation were decreased. Both apoptosis and ROS were significantly increased in the combination group compared with the radiation only group. Moreover, N-acetyl-L-cysteine, a scavenger of intracellular ROS, reversed the apoptosis and ROS induced by 1α,25(OH)2D3, indicating that 1α,25(OH)2D3 enhanced the radiosensitivity of cancer cells in vitro by promoting ROS-induced apoptosis. Moreover, our results demonstrated that 1α,25(OH)2D3 promoted the ROS level via activating NADPH oxidase complexes, NOX4, p22phox, and p47phox. In addition, knockdown of the vitamin D receptor (VDR) abolished the radiosensitization of 1α,25(OH)2D3, which confirmed that 1α,25(OH)2D3 radiosensitized tumor cells that depend on VDR. Similarly, our study also evidenced that vitamin D3 enhanced the radiosensitivity of cancer cells in vivo and extended the overall survival of mice with tumors. In summary, these results demonstrate that 1α,25(OH)2D3 enhances the radiosensitivity depending on VDR and activates the NADPH oxidase-ROS-apoptosis axis. Our findings suggest that 1α,25(OH)2D3 in combination with radiation enhances lung and ovarian cell radiosensitivity, potentially providing a novel combination therapeutic strategy.

Evaluation of the biomedical properties of a Ca+-conjugated silk fibroin porous material.

Hemostatic materials could reduce avertible death from bleeding during surgery and emergency treatment. To this end, silk fibroin (SF) loaded with Ca2+ (1.8, 3.6 5.4, or 7.2%, w:w) was tested as a new hemostatic material (designated as SF1.8, SF3.6, SF5.4, or SF7.2), and the Ca2+ release rate, platelet adhesion, blood coagulation, cytocompatibility, and antimicrobial properties were investigated. Platelet adhesion on SF1.8 was improved significantly compared with pure SF porous material, and increased with increasing Ca2+ concentration. For SF3.6, platelet adhesion was greater than observed for gelatin and calcium alginate porous materials, clotting occurred earlier, and the complete coagulation time was shorter. Additionally, rabbit ear wound studies revealed that the hemostatic time for SF3.6 was significantly shorter than for gelatin, and similar to that for calcium alginate. The shed blood weight was lowest when SF was loaded with 7.2% Ca2+. The SF3.6 porous material displayed no obvious cytotoxicity, and exhibited satisfactory antibacterial activity against Escherichia coli and Staphylococcus aureus.

Radon induced mitochondrial dysfunction in human bronchial epithelial cells and epithelial-mesenchymal transition with long-term exposure.

Radon is a naturally occurring radionuclide, which has a wide environmental distributed. It emits multiple high linear energy transfer (LET) alpha particles during radiative decay, and has been regarded as a human carcinogen by the International Agency for Research on Cancer. Currently, residential radon exposure is considered as the second highest cause of lung cancer and the leading cause among nonsmokers. Radon exposure leads to genomic instability, which causes the accumulation of multiple genetic changes and leads to cancer development. However, the molecular basis underlying carcinogenesis, especially the radon-induced changes to mitochondria, has not been fully elucidated. The aim of this study was to explore the dynamic changes in mitochondria along with the cell transformations induced by long-term radon exposure. A malignant transformation model of BEAS-2B cells was established with upto 40 times the usual radon exposure (20 000 Bq m-3, 30 min each time every 3 days). Long-term radon exposure induced EMT-like transformation of epithelial cells in our study, evidenced by decrease in epithelial markers and increase in mesenchymal markers, as well as the loss of cell-cell adhesion and alterations to the morphology of cells from compact shape to a spindle shaped, fibroblast-like morphology. Additionally, the proliferation and migration of cells were increased and apoptosis was decreased with long-term radon exposure. Furthermore, mitochondrial function was up-regulated and the levels of oxidative stress were repressed with long-term radon exposure. Our work explored the dynamic changes of mitochondrial in radon induced malignant transformation of lung bronchial epithelial cells, which could partially elucidate the role of mitochondria in radon induced cell malignancy.