Mitochondrial Modulation of Apoptosis Induced by Low-dose Radiation in Mouse Testicular Cells

Objective To investigate whether apoptosis induced by low-dose radiation （LDR） is regulated by mitochondrial pathways in testicular cells. Methods Male mice were exposed to whole-body LDR, and changes in mitochondrial function and in expression of apoptotic factors were analyzed in the testicular cells as follows. Total nitric-oxide synthase （T-NOS） and Na＋/K＋ ATPase activities were biochemically assayed. Reactive oxygen species （ROS） and mitochondrial membrane potential （Adjm） were determined by flow cytometry using fluorescent probes. Levels of mRNAs encoding cytochrome c （Cyt c） and apoptosis-inducing factor （AIF） were quantified by real-time reverse-transcription PCR （RT-PCR）. Expression of Cyt c, AIF, caspase-9, and caspase-3 at the protein level was assessed by western blotting and immunohistochemistry. Results LDR induced an increase in T-NOS activity and ROS levels, and a decrease in Na＋/K~ ATPase activity and mitochondrial A^m, in the testicular cells. The intensity of these effects increased with time after irradiation and with dose. The cells showed remarkable swelling and vacuolization of mitochondria, and displayed a time- and dose-dependent increase in the expression of Cyt c, AIF, procaspase-9, and procaspase-3. Activation of the two procaspases was confirmed by detection of the cleaved caspases. The changes in expression of the four apoptotic factors were mostly limited to spermatogonia and spermatocytes. Conclusion LDR can induce testicular cell apoptosis through mitochondrial signaling pathways

Effect of low-dose radiation on thyroid function and the gut microbiota

BACKGROUND The thyroid-gut axis has a great influence on the maintenance of human health;however,we know very little about the effects of low-dose ionizing radiation(LDR) on thyroid hormone levels and gut microbiota composition.AIM To investigate the potential effects of low-dose X-ray radiation to male C57BL/6J mice.METHODS Peripheral blood was collected for enzyme-linked immunosorbent assay(ELISA),and stool samples were taken for 16S ribosomal RNA(rRNA) gene sequencing after irradiation.RESULTS We found that LDR caused changes in thyroid stimulating hormone(TSH) levels in the irradiated mice,suggesting a dose-dependent response in thyroid function to ionizing radiation.No changes in the diversity and richness of the gut microbiota were observed in the LDR-exposed group in comparison to the controls.The abundance of Moraxellaceae and Enterobacteriaceae decreased in the LDR-exposed groups compared with the controls,and the Lachnospiraceae abundance increased in a dose-dependent manner in the radiated groups.And the abundances of uncultured_bacterium_g_Acinetobacter,uncultured_bacterium_o_Mollicutes_RF39,uncultured_bacterium_g_Citrobacter,and uncultured_bacterium_g_Lactococcus decreased in the radiated groups at the genus level,which showed a correlation with radiation exposure and diagnostic efficacy.Analysis of functional metabolic pathways revealed that biological metabolism was predicted to have an effect on functional activities,such as nucleotide metabolism,carbohydrate metabolism,and glycan biosynthesis and metabolism.Furthermore,Kyoto Encyclopedia of Genes and Genomes pathway annotation also suggested that changes in the gut microbiota were related to processing functions,including translation,replication and repair.CONCLUSION LDR can change thyroid function and the gut microbiota,and changes in the abundances of bacteria are correlated with the radiation dose.

Involvement of Endoplasmic Reticulum Stress in Apoptosis of Testicular Cells Induced by Low-dose Radiation

Summary： The study examined the role of endoplasmic reticulum stress （ERS） and signaling pathways of inositol-requiring enzyme-1 （IRE1）, RNA-activated protein kinase-like ER kinase （PERK） and activating transcription factor-6 （ATF6） in apoptosis of mouse testicular cells treated with low-dose radiation （LDR）. In the dose-dependent experiment, the mice were treated with whole-body X-ray irradiation at different doses （25, 50, 75, 100 or 200 mGy） and sacrificed 12 h later. In the time-dependent experiment, the mice were exposed to 75 mGy X-ray irradiation and killed at different time points （3, 6, 12, 18 or 24 h）. Testicular cells were harvested for experiments. H202 and NO concentrations, and Ca2＋-ATPase activity were detected by biochemical assays, the calcium ion concentration （[Ca2＋]i） by flow cytometry using fluo-3 probe, and GRP78 mRNA and protein expressions by quantitative real-time RT-PCR （qRT-PCR） and Western blotting, respectively. The mRNA expressions of S-XBP1, JNK, caspase-12 and CHOP were measured by qRT-PCR, and the protein expressions of IREla, S-XBP1, p-PERK, p-elF2a, ATF6 p50, p-JNK, pro-caspase-12, cleaved caspase-12 and CHOP by Western blot- ting. The results showed that the concentrations of H202 and NO, the mR_NA expressions of GRP78, S-XBP1, JNK, caspase-12 and CHOP, and the protein expressions of GRP78, S-XBP1, IREla, p-PERK, p-elF2a, ATF6 p50, p-JNK, pro-caspase-12, cleaved caspase-12 and CHOP were significantly increased in a time- and dose-dependent manner after LDR. But the [Ca2]i and Ca2-ATPase activities were sig nificantly decreased in a time and dose-dependent manner. It was concluded that the ERS, regulated by IRE 1, PERK and ATF6 pathways, is involved in the apoptosis of testicular cells in LDR mice, which is associated with ERS-apoptotic signaling molecules of JNK, caspase-12 and CHOP.

Low-dose radiation on spinal cord might be a new therapy for intractable chronic cancer and non-cancer pain

Intractable chronic pain is a great challenge in clinic.Central sensitization based on the positive changes of dendritic spines is the main mechanism of intractable chronic pain.And low-dose radiation has been proved to regulate the changes of dendritic spines negatively.Hence,we make a hypothesis that low-dose radiation could relieve cancer and noncancer pain through negatively regulating the shape and reducing the number and density of dendritic spines in the spinal cord.This method is supposed to be a new therapy for intractable chronic pain by expanding indication to non-cancer pain,translocating radiation site from where the tumor exists to special segments of spinal cord and keeping radiation dose at a low level.This therapy would be reliable for relieving non-cancer pain and supply more choices for relieving cancer pain.

Low-Dose Gamma Radiation Fields Decrease Cell Viability, Damage DNA, and Increase the Expression of Hsp70 and p53 Proteins in Human Leukocytes

Ionizing radiations are tools in diagnosis and treatment of diseases. Leukopenia from exposure to ionizing radiation has been reported. Due to their radiosensitivity, leukocytes are a biological model to analyze cell damage. Therefore, cell viability, DNA damage, and Hsp70 and p53 expression in human leukocytes exposed to low-dose gamma radiation fields from a 137Cs source were evaluated. A decrease in cell viability, DNA damage and an increase in the expression of Hsp70 and p53 proportional to the radiation dose received was found, which was 0.2, 0.4, 0.6, 0.8 and 1.0 mGy.

Local low-dose X-ray radiation promotes homing of mesenchymal stem cells to the injured mouse spinal cord

BACKGROUND： Bone marrow-derived mesenchymal stem cells （BMSCs） are a potentially useful source for cell replacement therapy following spinal cord injury. However, the homing characteristics of BMSCs in vivo remain unclear. Low-dose radiation has been shown to promote homing of BMSCs to exposed sites. OBJECTIVE： To investigate the effects of low-dose local radiation to non-injured areas on the ability of human BMSCs to home to the injured mouse spinal cord, as well as recovery of spinal cord injury. DESIGN, TIME AND SE＇I-FING： A randomized, controlled, animal experiment was performed at the Central Laboratory, Second Affiliated Hospital of Soochow University between October 2007 and October 2008. MATERIALS： BMSCs were isolated from four adult, human donors. METHODS： Fifty adult, female, Balb/c mice were subjected to adjusted weight-drop impact resulting in complete paraplegia. Three days later, mice were randomly assigned to a radiation ＋ transplantation group （n = 23） and a transplantation group （n = 20）. In total, 2 x 106 carboxyfluorescein diacetate succinimidyl ester-labeled BMSCs were injected into each mouse via the caudal vein. Mice in the radiation ＋ transplantation group received 2.5 Gy local X-ray irradiation 2 hours before BMSCs injection. MAIN OUTCOME MEASURES： The homing of BMSCs to injured cord and irradiated skin after transplantation was observed by fluorescence microscope; the structure recovery of injured cord was assessed by magnetic resonance imaging. RESULTS： Compared with the transplantation group, at 24 hours after transplantation, the number of BMSCs was significantly increased in the injured area and the exposed site （P 〈 0.05）, and inflammation and edema were significantly alleviated in the injured cord in the radiation ＋ transplantation group. CONCLUSION： Local low-dose radiation has the potential to promote homing of BMSCs and recovery of spinal cord injury, although the radiated region was not injured area.

Efficacy and safety of low-dose cyclophosphamide combined with lenvatinib, pembrolizumab and TACE for unresectable hepatocellular carcinoma:A single-center, prospective,single-arm clinical trial

Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenvatinib, pembrolizumab and transarterial chemoembolization(TACE) for the treatment of uHCC.Methods: From February 2022 to November 2023, a total of 40 patients diagnosed with uHCC were enrolled in this small-dose, single-center, single-arm, prospective study. They received a combined treatment of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE. Study endpoints included progression-free survival(PFS), objective response rate(ORR), and safety assessment. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors(mRECIST), while survival analysis was conducted through KaplanMeier curve analysis for overall survival(OS) and PFS. Adverse events(AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events(version 5.0).Results: A total of 34 patients were included in the study. The median follow-up duration was 11.2 [95% confidence interval(95% CI), 5.3-14.6] months, and the median PFS(mPFS) was 15.5(95% CI, 5.4-NA) months.Median OS(mOS) was not attained during the study period. The ORR was 55.9%, and the disease control rate(DCR) was 70.6%. AEs were reported in 27(79.4%) patients. The most frequently reported AEs(with an incidence rate >10%) included abnormal liver function(52.9%), abdominal pain(44.1%), abdominal distension and constipation(29.4%), hypertension(20.6%), leukopenia(17.6%), constipation(17.6%), ascites(14.7%), and insomnia(14.7%). Abnormal liver function(14.7%) had the most common grade 3 or higher AEs.Conclusions: A combination of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE is safe and effective for u HCC, showcasing a promising therapeutic strategy for managing uHCC.

Selective internal radiation therapy segmentectomy:A new minimally invasive curative option for primary liver malignancies?

Transarterial radioembolization or selective internal radiation therapy(SIRT)has emerged as a minimally invasive approach for the treatment of tumors.This percutaneous technique involves the local,intra-arterial delivery of radioactive microspheres directly into the tumor.Historically employed as a palliative measure for liver malignancies,SIRT has gained traction over the past decade as a potential curative option,mirroring the increasing role of radiation segmentectomy.The latest update of the BCLC hepatocellular carcinoma guidelines recognizes SIRT as an effective treatment modality comparable to other local ablative methods,particularly well-suited for patients where surgical resection or ablation is not feasible.Radiation segmentectomy is a more selective approach,aiming to deliver high-dose radiation to one to three specific hepatic segments,while minimizing damage to surrounding healthy tissue.Future research efforts in radiation segmentectomy should prioritize optimizing radiation dosimetry and refining the technique for super-selective administration of radiospheres within the designated hepatic segments.

Visualizing the Spin & Radiation of the Extended Electron in Magnetic Field

This article presents illustrations of an extended model of the electron to visualize how it spins and radiates in the external magnetic field. A time-varying magnetic field B produces a rotational induced electric field E which rotates (spins) the electron about its axis. In time-constant magnetic field: the electron radiates the cyclotron radiation. In time-varying magnetic field: synchrotron radiation is generated. The couplings between spin, acceleration and radiation will be discussed.

Heuristic Estimation of the Vacuum Energy Density of the Universe: Part II-Analysis Based on Frequency Domain Electromagnetic Radiation

In Part I of this paper, an inequality satisfied by the vacuum energy density of the universe was derived using an indirect and heuristic procedure. The derivation is based on a proposed thought experiment, according to which an electron is accelerated to a constant and relativistic speed at a distance L from a perfectly conducting plane. The charge of the electron was represented by a spherical charge distribution located within the Compton wavelength of the electron. Subsequently, the electron is incident on the perfect conductor giving rise to transition radiation. The energy associated with the transition radiation depends on the parameter L. It was shown that an inequality satisfied by the vacuum energy density will emerge when the length L is pushed to cosmological dimensions and the product of the radiated energy, and the time duration of emission is constrained by Heisenberg’s uncertainty principle. In this paper, a similar analysis is conducted with a chain of electrons oscillating sinusoidally and located above a conducting plane. In the thought experiment presented in this paper, the behavior of the energy radiated by the chain of oscillating electrons is studied in the frequency domain as a function of the length L of the chain. It is shown that when the length L is pushed to cosmological dimensions and the energy radiated within a single burst of duration of half a period of oscillation is constrained by the fact that electromagnetic energy consists of photons, an inequality satisfied by the vacuum energy density emerges as a result. The derived inequality is given by where is the vacuum energy density. This result is consistent with the measured value of the vacuum energy density, which is 5.38 × 10-10 J/m. The result obtained here is in better agreement with experimental data than the one obtained in Part I of this paper with time domain radiation.

The Effect of a Monatomic Layer on a Surface on the Transition Radiation

The transition radiation of a charged particle crossing the interface of two media having a monatomic impurity layer is investigated. It is shown that at sliding angles of incidence of a particle on the boundary of the media, the transition radiation is mainly determined by the properties of the surface layer. The possibility of using transition radiation to study the surface of substances is discussed. In addition, due to the hard radiation present in space, this research may be important for the use of light monoatomic layers as a material for satellite antennas, “solar sails” and cover layers in a future space (interstellar) mission.

A Quasi-Linear Relationship between Planetary Outgoing Longwave Radiation and Surface Temperature in a Radiative-Convective-Transportive Climate Model of a Gray Atmosphere

In this study,we put forward a radiative-convective-transportive energy balance model of a gray atmosphere to examine individual roles of the greenhouse effect of water vapor,vertical convection,and atmospheric poleward energy transport as well as their combined effects for a quasi-linear relationship between the outgoing longwave radiation(OLR)and surface temperature(T_(S)).The greenhouse effect of water vapor enhances the meridional gradient of surface temperature,thereby directly contributing to a quasi-linear OLR-T_(S) relationship.The atmospheric poleward energy transport decreases the meridional gradient of surface temperature.As a result of the poleward energy transport,tropical(high-latitude)atmosphere-surface columns emit less(more)OLR than the solar energy input at their respective locations,causing a substantial reduction of the meridional gradient of the OLR.The combined effect of reducing the meridional gradients of both OLR and surface temperature by the poleward energy transport also contributes to the quasi-linear OLR-T_(S) relationship.Vertical convective energy transport reduces the meridional gradient of surface temperature without affecting the meridional gradient of OLR,thereby suppressing part of the reduction to the increasing rate of OLR with surface temperature by the greenhouse effect of water vapor and poleward energy transport.Because of the nature of the energy balance in the climate system,such a quasi-linear relationship is also a good approximation for the relationship between the annual-mean net downward solar energy flux at the top of the atmosphere and surface temperature.

Predicting microseismic,acoustic emission and electromagnetic radiation data using neural networks

Microseism,acoustic emission and electromagnetic radiation(M-A-E)data are usually used for predicting rockburst hazards.However,it is a great challenge to realize the prediction of M-A-E data.In this study,with the aid of a deep learning algorithm,a new method for the prediction of M-A-E data is proposed.In this method,an M-A-E data prediction model is built based on a variety of neural networks after analyzing numerous M-A-E data,and then the M-A-E data can be predicted.The predicted results are highly correlated with the real data collected in the field.Through field verification,the deep learning-based prediction method of M-A-E data provides quantitative prediction data for rockburst monitoring.

Scheme of negative acoustic radiation force based on a multiple-layered spherical structure

Acoustic radiation force(ARF), as an important particle manipulation method, has been extensively studied in recent years. With the introduction of the concept of “acoustic tweezers”, negative acoustic radiation has become a research hotspot. In this paper, a scheme of realizing negative ARF based on the multiple-layered spherical structure design is proposed. The specific structure and design idea are presented. Detailed theoretical calculation analysis is carried out.Numerical simulations have been performed to verify the correctness of this prediction. The conjecture that the suppression of backscattering can achieve negative ARF is verified concretely, which greatly expands the application prospect and design ideas of the ARF. This work has laid a theoretical foundation for realizing precise control of the structure.

A statistical analysis of the Kappa-type energy spectrum distribution of radiation belt electrons observed by Van Allen Probes

The energy spectrum of energetic electrons is a key factor representing the dynamic variations of Earth’s Van Allen radiation belts.Increased measurements have indicated that the commonly used Maxwellian and Kappa distributions are inadequate for capturing the realistic spectral distributions of radiation belt electrons.Here we adopt the Kappa-type(KT)distribution as the fitting function and perform a statistical analysis to investigate the radiation belt electron flux spectra observed by the Van Allen Probes.By calculating the optimal values of the key KT distribution parameters(i.e.,κandθ2)from the observed spectral shapes,we fit the radiation belt electron fluxes at different L-shells under different geomagnetic conditions.In this manner,we obtain typical values of the KT distribution parameters,which are statistically feasible for modeling the radiation belt electron flux profiles during either geomagnetically quiet or active periods.A comparison of the KT distribution model results with those using the Maxwellian or Kappa distribution reveals the advantage of the KT distribution for studying the overall properties of the radiation belt electron spectral distribution,which has important implications for deepening the current understanding of the radiation belt electron dynamics under evolving geomagnetic conditions.

Isomeric fluorescence sensors for wide range detection of ionizing radiations

In order to achieve a wider range of ionizing radiations detection,novel fluorescence sensing materials have been developed that utilize the fluorescence enhancement phenomenon caused by the intramolecular photoinduced electron transfer(PET)effect.Two perylene diimide isomers PDI-P and PDI-B were designed and synthesized,and their molecular structures were characterized by high-resolution Fourier transform mass spectrometry(HRMS),nuclear magnetic resonance hydrogen and carbon spectroscopy(~1H and~(13)C NMR).The interaction between ionizing radiation and fluorescent molecules was simulated by HCl titration.The results show that combining PDIs and HCl can improve fluorescence through the retro-PET process.Despite the similarities in chemical structures,the fluorescent enhancement multiple of PDI-B with aromatic amine as electron donor is much higher than that of PDI-P with alkyl amine.In the direct irradiation experiments of ionizing radiation,the emission enhancement multiples of PDI-P and PDI-B are 2.01 and 45.4,respectively.Furthermore,density functional theory(DFT)and time-dependent density functional theory(TDDFT)calculations indicate that the HOMO and HOMO-1 energy ranges of PDI-P and PDI-B are 0.54 e V and 1.13 e V,respectively.A wider energy range has a stronger driving force on electrons,which is conducive to fluorescence quenching.Both femtosecond transient absorption spectroscopy(fs-TAS)and transient fluorescence spectroscopy(TFS)tests show that PDI-B has shorter charge separation lifetime and higher electron transfer rate constant.Although both isomers can significantly reduce LOD during PET process,PDI-B with aromatic amine has a wider detection range of 0.118—240 Gy due to its larger emission enhancement,which is a leap of three orders of magnitude.It breaks through the detection range of gamma radiation reported in existing studies,and provides theoretical support for the further study of sensitive and effective new materials for ionizing radiation detection.

Effect of surface modification on the radiation stability of diamond ohmic contacts

The ohmic contact interface between diamond and metal is essential for the application of diamond detectors.Surface modification can significantly affect the contact performance and eliminate the interface polarization effect.However,the radiation stability of a diamond detector is also sensitive to surface modification.In this work,the influence of surface modification technology on a diamond ohmic contact under high-energy radiation was investigated.Before radiation,the specific contact resistivities(ρc)between Ti/Pt/Au-hydrogen-terminated diamond(H-diamond)and Ti/Pt/Au-oxygenterminated diamond(O-diamond)were 2.0×10^(-4)W·cm^(2) and 4.3×10^(-3)Wcm^(2),respectively.After 10 MeV electron radiation,the ρc of Ti/Pt/Au H-diamond and Ti/Pt/Au O-diamond were 5.3×10^(-3)W·cm^(2)and 9.1×10^(-3)W·cm^(2),respectively.The rates of change of ρc of H-diamond and O-diamond after radiation were 2550%and 112%,respectively.The electron radiation promotes bond reconstruction of the diamond surface,resulting in an increase in ρc.

Electronic effects on radiation damage inα-iron:A molecular dynamics study

Iron(Fe)-based alloys,which have been widely used as structural materials in nuclear reactors,can significantly change their microstructure properties and macroscopic properties under high flux neutron irradiation during operation,thus,the problems associated with the safe operation of nuclear reactors have been put forward naturally.In this work,a molecular dynamics simulation approach combined with electronic effects is developed for investigating the primary radiation damage process inα-Fe.Specifically,the influence of electronic effects on the collision cascade in Fe is systematically evaluated based on two commonly used interatomic potentials for Fe.The simulation results reveal that both electronic stopping(ES)and electron-phonon coupling(EPC)can contribute to the decrease of the number of defects in the thermal spike phase.The application of ES reduces the number of residual defects after the cascade evolution,whereas EPC has a reverse effect.The introduction of electronic effects promotes the formation of the dispersive subcascade:ES significantly changes the geometry of the damaged region in the thermal spike phase,whereas EPC mainly reduces the extent of the damaged region.Furthermore,the incorporation of electronic effects effectively mitigates discrepancies in simulation outcomes when using different interatomic potentials.

Molecular dynamics study of primary radiation damage in TiVTa concentrated solid-solution alloy

The primary radiation damage in pure V and TiVTa concentrated solid-solution alloy(CSA)was studied using a molecular dynamics method.We have performed displacement cascade simulations to explore the generation and evolution behavior of irradiation defects.The results demonstrate that the defect accumulation and agglomeration in TiVTa CSA are significantly suppressed compared to pure V.The peak value of Frenkel pairs during cascade collisions in TiVTa CSA is much higher than that in pure V due to the lower formation energy of point defects.Meanwhile,the longer lifetime of the thermal spike relaxation and slow energy dissipation capability of TiVTa CSA can facilitate the recombination of point defects.The defect agglomeration rate in TiVTa CSA is much lower due to the lower binding energy of interstitial clusters and reduced interstitial diffusivity.Furthermore,the occurrence probability of dislocation loops in TiVTa CSA is lower than that in pure V.The reduction in primary radiation damage may enhance the radiation resistance of TiVTa CSA,and the improved radiation tolerance is primarily attributed to the relaxation stage and long-term defect evolution rather than the ballistic stage.These results can provide fundamental insights into irradiation-induced defects evolution in refractory CSAs.

Combinational therapy with Myc decoy oligodeoxynucleotides encapsulated in nanocarrier and X-irradiation on breast cancer cells

The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line.Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene.The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical properties.Moreover,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer cells.All anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately.It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment.It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.