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Ionizing radiation poses significant risks to astronauts during deep space exploration. This study investigates the impact of radiation on nucleophosmin (NPM), a protein involved in DNA repair, cell cycle regulation, and proliferation. Using X-rays, a common space radiation, we found that radiation suppresses NPM expression. Knockdown of NPM increases DNA damage after irradiation, disrupts cell cycle distribution and enhances cellular radiosensitivity. Additionally, NPM interacts with globular actin (G-actin), affecting its translocation and centrosome binding during mitosis. These findings provide insights into the role of NPM in cellular processes in responding to radiation. This article enhances our comprehension of radiation-induced genomic instability and provides a foundational platform for prospective investigations within the realm of space radiation and its implications for cancer therapy.

FLASH radiotherapy (FLASH-RT) is a new strategy for tumor treatment with an ultra-high dose rate of more than 40 ​Gy/s. Compared with conventional radiotherapy (CONV-RT), FLASH-RT has no different inhibitory effects on tumors but less damage to normal tissues, which is called the “spare” effect. The “spare” effect triggers our exploration of the great prospect of subverting conventional radiotherapy and its intricate mechanisms. Mitochondrial homeostasis, the immune microenvironment, or DNA integrity may potentially represent the primary breakthrough direction in understanding the mechanisms. Concurrently, it is imperative to advance timely clinical translation efforts. Clinical trials of FLASH-RT have progressed to Phase II in both the United States and Switzerland, with current findings suggesting that FLASH-RT achieves comparable efficacy to CONV-RT while mitigating side effects in select cancer cell types. While summarizing the existing FLASH experiments, this paper emphasizes the significance of clinical transformation and the challenges that will be faced and proposes possible solutions.

As an attractive transition approach, the altitude-hold transition is a special type of super-maneuvering and the vertical/horizontal flight mode transition that an agile aircraft conducts at fixed altitude. However, it is still challenging to implement an autonomous control of the altitude-hold transition while the existing optimal transition planning methods cannot avoid an evident altitude change during the transition process. This paper proposes a corridor-based flight mode transition strategy and presents a successful flight demonstration of the altitude-hold transition on a small ducted-fan tail-sitter unmanned aerial vehicle. In the proposed corridor-based methodology, we model and analyze the transition corridor, concentrate on the dynamic characteristics of the altitude-hold transition, and emphasize that a valid transition trajectory should be governed by its transition corridor. The identified transition corridor reveals that for a given velocity trajectory, the solution for the corresponding trajectories of pitch angle and thrust is unique. Based on this, the transition trajectory generation problem is addressed simply on the velocity-acceleration plane. Furthermore, a proper flight control scheme is devised to track the generated transition trajectories. Finally, the effectiveness of the proposed method is verified through practical flight tests, in which the altitude change is less than 1.1 m during the entire transition course.

Aneuploidy is a hallmark of genomic instability that leads to tumor initiation, progression, and metastasis. CDC20, Bub1, and Bub3 form the mitosis checkpoint complex (MCC) that binds the anaphase-promoting complex or cyclosome (APC/C), a crucial factor of the spindle assembly checkpoint (SAC), to ensure the bi-directional attachment and proper segregation of all sister chromosomes. However, just how MCC is regulated to ensure normal mitosis during cellular division remains unclear. In the present study, we demonstrated that LNC CRYBG3, an ionizing radiation-inducible long noncoding RNA, directly binds with Bub3 and interrupts its interaction with CDC20 to result in aneuploidy. The 261–317 (S3) residual of the LNC CRYBG3 sequence is critical for its interaction with Bub3 protein. Overexpression of LNC CRYBG3 leads to aneuploidy and promotes tumorigenesis and metastasis of lung cancer cells, implying that LNC CRYBG3 is a novel oncogene. These findings provide a novel mechanistic basis for the pathogenesis of NSCLC after exposure to ionizing radiation as well as a potential target for the diagnosis, treatment, and prognosis of an often fatal disease.

Lung cancer is one of the highest health risks caused by ionizing radiation, which induces both direct effects and non-targeted effects. However, whether radiation-induced non-targeted effects result in epithelial-mesenchymal transition, a critical process during tumorigenesis, in non-targeted lung tissues remains unknown. In the present study, Kunming mice were subjected to whole-body, cranial or local abdominal irradiation of single-dose or fractionated 4 Gy X-rays, and the expressions of epithelial-mesenchymal transition markers in non-targeted lung tissues were assessed by both qRT-PCR and immunofluorescent staining. It was found that the epithelial marker was downregulated while the mesenchymal markers were upregulated significantly in non-targeted lung tissues of the irradiated mice. Local abdominal irradiation was more efficient in inducing epithelial-mesenchymal transition than whole-body or cranial irradiation when the fractionated irradiation method was adopted. In addition, the intraperitoneal administration of celecoxib suppressed epithelial-mesenchymal transition in the non-targeted lung tissues. In conclusion, our findings suggest that epithelial-mesenchymal transition is induced in non-targeted lung tissues, but can be suppressed by inhibition of cyclooxygenase-2 by celecoxib.

ABSTRACTRadiation-induced lung injury (RILI) occurs most often in radiotherapy of lung cancer, esophageal cancer, and other thoracic cancers. The occurrence of RILI is a complex process that includes a variety of cellular and molecular interactions, which ultimately result in carcinogenesis. However, the underlying mechanism is unknown. Here we show that Ras-related C3 botulinum toxin substrate 2 (RAC2) and transcription factor jun-B (JUNB) were upregulated in non-small cell carcinoma (NSCLC) tissues and were associated with poor prognoses for NSCLC patients. Ionizing radiation also caused increased expression of RAC2 in quiescent stage cells, and the reentry of quiescent cells into a new cell cycle. The activity of the serum response factor (SRF) was activated by RAC2and other Rho family genes (RhoA, ROCK, and LIM kinase). Consequently, JUNBacted as an oncogene and induced abnormal proliferation of quiescent cells. Together, the results showed that RAC2can be used as a target gene for radiation protection. A better understanding of the RAC2and JUNBmechanisms in the molecular etiology of lung cancer will be helpful in reducing cancer risks and side effects during treatment of this disorder. Our study therefore provides a new perspective on the involvement of RAC2and JUNBas oncogenes in the tumorigenesis of NSCLC.

Radiation-induced bone loss is a potential health concern for cancer patients undergoing radiotherapy. Enhanced bone resorption by osteoclasts and decreased bone formation by osteoblasts were thought to be the main reasons. In this study, we showed that both pre-differentiating and differentiating osteoclasts were relatively sensitive to X-rays compared with osteoblasts. X-rays decreased cell viability to a greater degree in RAW264.7 cells and in differentiating cells than than in osteoblastic MC3T3-E1 cells. X-rays at up to 8 Gy had little effects on osteoblast mineralization. In contrast, X-rays at 1 Gy induced enhanced osteoclastogenesis by enhanced cell fusion, but had no effects on bone resorption. A higher dose of X-rays at 8 Gy, however, had an inhibitory effect on bone resorption. In addition, actin ring formation was disrupted by 8 Gy of X-rays and reorganized into clusters. An increased activity of Caspase 3 was found after X-ray exposure. Actin disorganization and increased apoptosis may be the potential effects of X-rays at high doses, by inhibiting osteoclast differentiation. Taken together, our data indicate high radiosensitivity of osteoclasts. X-ray irradiation at relatively low doses can activate osteoclastogenesis, but not osteogenic differentiation. The radiosensitive osteoclasts are the potentially responsive cells for X-ray-induced bone loss.

ABSTRACTOur recent study showed that quiescent G0 cells are more resistant to ionizing radiation than G1 cells; however, the underlying mechanism for this increased radioresistance is unknown. Based on the relatively lower DNA damage induced in G0 cells, we hypothesize that these cells are exposed to less oxidative stress during exposure. As a catalytic subunit of NADPH oxidase, Ras-related C3 botulinum toxin substrate 2 (RAC2) may be involved in the cellular response to ionizing radiation. Here, we show that RAC2 was expressed at low levels in G0 cells but increased substantially in G1 cells. Relative to G1 cells, the total antioxidant capacity in G0 phase cells increased upon exposure to X-ray radiation, whereas the intracellular concentration of ROS and malondialdehyde increased only slightly. The induction of DNA single- and double-stranded breaks in G1 cells by X-ray radiation was inhibited by knockdown of RAC2. P38 MAPK interaction with RAC2 resulted in a decrease of functional RAC2. Increased phosphorylation of P38 MAPK in G0 cells also increased cellular radioresistance; however, excessive production of ROS caused P38 MAPK dephosphorylation. P38 MAPK, phosphorylated P38 MAPK, and RAC2 regulated in mutual feedback and negative feedback regulatory pathways, resulting in the radioresistance of G0 cells.

This paper presents a new method for simultaneous synthesis of dynamic controller and static anti-windup compensator for saturated Lipschitz systems. Thanks to the reformulated Lipschitz property, the Lipschitz systems can be transformed into LPV (linear parameter-varying) systems whose system matrices are affine in a parameter matrix. Based on the modified sector condition dealing with saturation nonlinearity, the design of a nonlinear anti-windup-based controller leads to the solvability of a set of bilinear matrix inequalities (BMI) on the vertices of a bounded convex set which can be solved by the so-called iterative linear matrix inequality (ILMI) algorithm. A numerical example is presented to illustrate the effectiveness of the proposed method.

This paper presents a new method for simultaneous synthesis of dynamic controller and static anti-windup compensator for saturated Lipschitz systems. Thanks to the reformulated Lipschitz property, the Lipschitz systems can be transformed into LPV (linear parameter-varying) systems whose system matrices are affine in a parameter matrix. Based on the modified sector condition dealing with saturation nonlinearity, the design of a nonlinear anti-windup-based controller leads to the solvability of a set of bilinear matrix inequalities (BMI) on the vertices of a bounded convex set which can be solved by the so-called iterative linear matrix inequality (ILMI) algorithm. A numerical example is presented to illustrate the effectiveness of the proposed method.

During a long-term exploration in space, astronauts will be constantly exposed to space radiation which contains various types of low dose-rate heavy particles. Although the fluxes of these heavy ions are very small, the heavy ions can cause severe biological effects including early effects and late effects. This short review will discuss the biological effects induced by space radiation and introduce a new anti-radiation agent we have developed. We synthesized a class of reactive oxygen species scavengers called GANRA-5 with lowly toxic but high radio-protective effect to both heavy ions and X-rays. GANRA-5 can protect cells from X-rays and carbon ions induced cell killing by significantly reducing the amount of free radical production therefor reduce double-strand breaks and genomic instability. In vivo, GANRA-5 can effectively protect the mice from the damage induced by X-rays irradiation by enhancing superoxide dismutase activities. In brief, GANRA-5 is potentially applicable in space flight.

Space exploration represents great challenge to astronauts’ health because of the uncertain risk of carcinogenesis caused by space radiation, in which high-charge and -energy (HZE) particles should be the most harmful components. Although there are a number of researches confirming that HZE particles have more severe biological effects including tumorigenesis than low-LET radiations, it is still very hard to accurately estimate the cancer risk of space HZE radiation due to the lack of suitable epidemiological data on exposures to low-dose HZE particle irradiation. Ground-based experiments on high-energy heavy ion accelerators might be appropriate complement for understanding the risk of space radiation. On the other hand, effective countermeasures to reduce the radiation damage are essential to manned space exploration. Up to now, shielding is still the most practical way to attenuate biological responses of space radiation. However, the knowledge on the biological effects of secondary particles produced by the interaction of HZE particles with shielding materials is required for space shielding design. This review will discuss the issues of space HZE particles and the biological effects of secondary particles produced by the interaction of space radiation and shielding materials.

Multiple objects tracking is a challenging task. This article presents an algorithm which can detect and track multiple objects, and update target model automatically. The contributions of this paper as follow: Firstly, we also use color histogram(CH) and histogram of orientated gradients(HOG) to represent the objects, model update is realized by kalman filter and gaussian model; secondly we use Gaussian Mixture Model(GMM) and Bhattacharyya distance to detect object appearance. Particle filter with combined features and model update mechanism can improve tracking results. Experiments on video sequences demonstrate that the method presented in this paper can realize multiple objects detection and tracking.

AbstractMultiple objects tracking is a challenging task. This article presents an algorithm which can detect and track multiple objects, and update target model automatically. The contributions of this paper as follow: Firstly,we also use color histogram(CH) and histogram of orientated gradients(HOG) to represent the objects, model update is realized by kalman filter and gaussian model; secondly we use Gaussian Mixture Model(GMM) and Bhattacharyya distance to detect object appearance. Particle filter with combined features and model update mechanism can improve tracking results. Experiments on video sequences demonstrate that the method presented in this paper can realize multiple objects detection and tracking.

Yaw control is significant to the attitude control of small unmanned helicopters (SUHs). Since the existing robust control method cannot be applied to the SUH with unknown dynamics and disturbances, this paper proposes an improved active disturbance rejection control (IADRC) to solve the problem. The IADRC obtains the optimal solution of the actuator gain (b0) by gradient descent. Besides, this paper summarizes some experiences during the tuning process of ADRC, which significantly reduces the difficulty of designing ADRC. Finally, the experimental results show that the proposed method is better than the traditional PID in robust and tracking control performance.

MicroRNA (miRNA), a small non-coding RNA molecule, is vital in genetic regulation, and miRNA pathway, which regulates gene expression through degradation or translational suppression of their target transcripts, is highly conservative in evolution. Although profiles of miRNAs are different in various cell types and tissues, miRNAs have been considered as a crucial class of regulators in cellular response to ionizing radiation (IR). By carrying out a series of experiments, we have found that altered transcriptional regulation network composed of radiation-mediated miRNAs regulates the expression of their downstream target genes in most biological processes to control cell growth, cell cycle and apoptosis. For example, the newly identified miR-3928 negatively regulates the expression of Dicer, which has been validated by the luciferase assay and western blotting. Dicer is not only a key participant in responding to radiation, but also a critical factor for the maturation of miRNAs, suggesting that miR-3928 affects on the expression of other miRNAs through regulating Dicer. Among the miRNAs controlled by the Dicer, we reveal that miR-185 and miR-663 can efficiently suppress ATR and TGF-β1 expression, which are both important responders in the process of radiobiological effects. Further experiments reveal that the expression of Dicer is suppressed by miR-3928 induced by IR and consequently, the maturation of other miRNAs including miR-185 and miR-663 is inhibited, resulting in the abundantly enhanced expression of ATR and TGF-β1 respectively. This mechanism to hammer at fixing DNA damage or promote cells to apoptosis caused by IR has important implications in the decision of cell fates. Moreover, it has been shown that the expression of BTG1 is characterized in response to factors that induce growth arrest and subsequent differentiation both in vivo and in vitro, affecting cellular physiological progresses of angiogenesis, follicular development and myoblast and B cell differentiation, through regulating cell growth, migration, cell cycle, apoptosis and differentiation. BTG1 gene is phylogenetically highly conserved in its coding and 3′-untranslated region (UTR), which is considered as a decisive element involved in regulation of BTG1 expression. We present evidence that BTG1 can be induced by IR and confirm that miR-454-3p, whose gene locates in the intron of Ska2 gene, can regulate BTG1 expression through directly binding to the 3′-UTR of BTG1 mRNA. These results point out that increased expression of BTG1 caused by the down-regulation of miR-454-3p in case that IR modulates endogenous activity of PRMT1, a BTG1-binding partner, which can methylate endogenous transcription factors to change gene expression pattern and reply radiostilumation. An inverse relationship between the levels of expression of BTG1 and miR-454-3p reveals that there exists a new pathway in response to IR stimulation. Furthermore, cell growth will be transiently increased by the knockdown of BTG1 by transfecting BTG1 siRNA or miR-454-3p mimic. However, the apoptotic state of cells can be tested after 2 days. Down-regulation of BTG1 by miR-454-3p increases the sensitivity of human renal cell carcinoma 786-O cells to IR-induced apoptosis, suggesting that BTG1 could serve as a terget for sensitizing renal carcinoma to standard radiotherapy. Taken together, all these data indicate that alteration of miRNA expression is evident in the cellular response to IR. MiR-3928, miR-185, miR-663 and miR-454-3p may constitute a complex network contributing to the regulation of radiobiological effects. It is apparent that the study of radiation-related miRNAs is beneficial to qualitatively and quantitatively modulating radiobiological effects, and also in favor of the advanced research of miRNA functions.

High atomic number and high-energy (HZE) particles in deep space are of low abundance but substantially contribute to the biological effects of space radiation. Shielding is so far the most effective way to partially protect astronauts from these highly penetrating particles. However, simulated calculations and measurements have predicted that secondary particles resulting from the shielding of cosmic rays produce a significant fraction of the total dose and dose equivalent. In this study, we investigated the biological effects of secondary radiation with two cell types, and with cells exposed in different phases of the cell cycle, by comparing the biological effects of a 200 MeV/u iron beam with a shielded beam in which the energy of the iron ion beam was decreased from 500 MeV/u to 200 MeV/u with PMMA, polyethylene (PE), or aluminum. We found that beam shielding resulted in increased induction of 53BP1 foci and micronuclei in a cell-type-dependent manner compared with the unshielded 200 MeV/u Fe ion beam. These findings provide experimental proof that the biological effects of secondary particles resulting from the interaction between HZE particles and shielding materials should be considered in shielding design.