Exploring the clinical significance of IL-38 correlation with PD-1, CTLA-4, and FOXP3 in colorectal cancer draining lymph nodes.

Introduction: Colorectal cancer (CRC) presents a substantial challenge characterized by unacceptably high mortality and morbidity, primarily attributed to delayed diagnosis and reliance on palliative care. The immune response of the host plays a pivotal role in carcinogenesis, with IL-38 emerging as a potential protective factor in CRC. However, the precise involvement of IL-38 among various leucocytes, its interactions with PD-1/PD-L1, and its impact on metastasis require further elucidation. Results: Our investigation revealed a significant correlation between IL-38 expression and metastasis, particularly concerning survival and interactions among diverse leucocytes within draining lymph nodes. In the mesentery lymph nodes, we observed an inverse correlation between IL-38 expression and stages of lymph node invasions (TNM), invasion depth, distance, and differentiation. This aligns with an overall survival advantage associated with higher IL-38 expression in CRC patients' nodes compared to lower levels, as well as elevated IL-38 expression on CD4+ or CD8+ cells. Notably, a distinct subset of patients characterized by IL-38high/PD-1low expression exhibited superior survival outcomes compared to other combinations. Discussion: Our findings demonstrate that IL-38 expression in colorectal regional nodes from CRC patients is inversely correlated with PD-1/PD-L1 but positively correlated with infiltrating CD4+ or CD8+ lymphocytes. The combined assessment of IL-38 and PD-1 expression in colorectal regional nodes emerges as a promising biomarker for predicting the prognosis of CRC.

CD64 plays a key role in diabetic wound healing.

Introduction: Wound healing poses a clinical challenge in diabetes mellitus (DM) due to compromised host immunity. CD64, an IgG-binding Fcgr1 receptor, acts as a pro-inflammatory mediator. While its presence has been identified in various inflammatory diseases, its specific role in wound healing, especially in DM, remains unclear. Objectives: We aimed to investigate the involvement of CD64 in diabetic wound healing using a DM animal model with CD64 KO mice. Methods: First, we compared CD64 expression in chronic skin ulcers from human DM and non-DM skin. Then, we monitored wound healing in a DM mouse model over 10 days, with or without CD64 KO, using macroscopic and microscopic observations, as well as immunohistochemistry. Results: CD64 expression was significantly upregulated (1.25-fold) in chronic ulcerative skin from DM patients compared to non-DM individuals. Clinical observations were consistent with animal model findings, showing a significant delay in wound healing, particularly by day 7, in CD64 KO mice compared to WT mice. Additionally, infiltrating CD163+ M2 macrophages in the wounds of DM mice decreased significantly compared to non-DM mice over time. Delayed wound healing in DM CD64 KO mice correlated with the presence of inflammatory mediators. Conclusion: CD64 seems to play a crucial role in wound healing, especially in DM conditions, where it is associated with CD163+ M2 macrophage infiltration. These data suggest that CD64 relies on host immunity during the wound healing process. Such data may provide useful information for both basic scientists and clinicians to deal with diabetic chronic wound healing.

The lncRNA FENDRR inhibits colorectal cancer progression via interacting with and triggering GSTP1 ubiquitination by FBX8.

Background: Colorectal cancer (CRC) is characterized by its aggressiveness and high fatality rate. Long noncoding RNAs (lncRNAs) as molecular scaffolding in CRC have received little attention. Methods: The TCGA database was used to find putative anti-oncogenic lncRNAs in CRC. The effect of FENDRR on CRC was evaluated using the colony formation assay, transwell assays, and wound healing assays, and FENDRR expression was validated by qRT-PCR. The location of the FENDRR binding proteins was determined by an RNA pull-down experiment, and the retrieved proteins were recognized by mass spectrometry. RNA immunoprecipitation (RIP) studies were used to demonstrate the interaction of GSTP1, FBX8, and FENDRR. Co-IP and immunofluorescence were utilized to confirm the connection between GSTP1 and FBX8. To determine the precise signaling pathways implicated in the action of FENDRR in CRC, we performed next-generation sequencing (NGS) on CRC cells transfected with a vector overexpressing FENDRR. Results: The expression of FENDRR was significantly downregulated in CRC tissue and cells. The results of the function experiments showed that overexpression of FENDRR reduced CRC cells' ability to proliferation, invasion, migration and tube formation. In terms of mechanism, FENDRR could bind both GSTP1 and FBX8, act as a molecular scaffold, and utilize FBX8 to regulate the stability of GSTP1's protein. Additionally, the outcomes of NGS and qRT-PCR demonstrated that the expression of genes linked to the HIF-1 pathway was down-regulated following FENDRR overexpression. Lastly, rescue tests demonstrated that overexpression of GSTP1 in CRC cells could completely restore the inhibition induced by FENDRR. Conclusion: In this study, we found that the molecular scaffolding protein FENDRR regulates the ubiquitination of GSTP1 and the suppression of the HIF-1 signaling pathway in the development of CRC. Our research provides more evidence of FENDRR's crucial role in the emergence of CRC and identifies it as a potential therapeutic target for CRC patients.

Autoinhibited kinesin-1 adopts a hierarchical folding pattern.

Conventional kinesin-1 is the primary anterograde motor in cells for transporting cellular cargo. While there is a consensus that the C-terminal tail of kinesin-1 inhibits motility, the molecular architecture of a full-length autoinhibited kinesin-1 remains unknown. Here, we combine crosslinking mass spectrometry (XL-MS), electron microscopy (EM), and AlphaFold structure prediction to determine the architecture of the full-length autoinhibited kinesin-1 homodimer (kinesin-1 heavy chain [KHC]) and kinesin-1 heterotetramer (KHC bound to kinesin light chain 1 [KLC1]). Our integrative analysis shows that kinesin-1 forms a compact, bent conformation through a break in coiled-coil 3. Moreover, our XL-MS analysis demonstrates that kinesin light chains stabilize the folded inhibited state rather than inducing a new structural state. Using our structural model, we show that disruption of multiple interactions between the motor, stalk, and tail domains is required to activate the full-length kinesin-1. Our work offers a conceptual framework for understanding how cargo adaptors and microtubule-associated proteins relieve autoinhibition to promote activation.

Long non-coding RNA FENDRR suppresses cancer-associated fibroblasts and serves as a prognostic indicator in colorectal cancer.

Genetically abnormal fibroblasts are notably more prevalent in colorectal cancer (CRC) than in adjacent normal tissue, emphasizing their significance in driving the heterogeneity of the tumor microenvironment. Functioning as a significant regulatory gene in the context of fibrosis, FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) has exhibited abnormal expression in colorectal cancer and interstitial localization in our experiments. However, current research on the role of FENDRR in cancer has focused solely on its impact on cancer cells. Its crucial role in the tumor stroma is yet to be explored. The goal of this study was to understand the relationship between atypical FENDRR expression, its distinct localization, and genetically abnormal fibroblasts in CRC. We aimed to establish the function of FENDRR within the stromal compartment of patients through bioinformatics. Our study confirmed that FENDRR suppresses cancer-associated fibroblasts by inhibiting their activation and collagen generation in CRC. Furthermore, our findings suggest that low FENDRR expression indicates a poor prognosis. Therefore, we propose that FENDRR is a promising therapeutic target for future studies in CRC.

Autoinhibited kinesin-1 adopts a hierarchical folding pattern.

Conventional kinesin-1 is the primary anterograde motor in cells for transporting cellular cargo. While there is a consensus that the C-terminal tail of kinesin-1 inhibits motility, the molecular architecture of a full-length autoinhibited kinesin-1 remains unknown. Here, we combine cross-linking mass spectrometry (XL-MS), electron microscopy (EM), and AlphaFold structure prediction to determine the architecture of the full-length autoinhibited kinesin-1 homodimer [kinesin-1 heavy chain (KHC)] and kinesin-1 heterotetramer [KHC bound to kinesin light chain 1 (KLC1)]. Our integrative analysis shows that kinesin-1 forms a compact, bent conformation through a break in coiled coil 3. Moreover, our XL-MS analysis demonstrates that kinesin light chains stabilize the folded inhibited state rather than inducing a new structural state. Using our structural model, we show that disruption of multiple interactions between the motor, stalk, and tail domains is required to activate the full-length kinesin-1. Our work offers a conceptual framework for understanding how cargo adaptors and microtubule-associated proteins relieve autoinhibition to promote activation.

Mesojunction-Based Design Paradigm of Structural DNA Nanotechnology.

Mesojunctions were introduced as a basic type of crossover configuration in the early development of structural DNA nanotechnology. However, the investigations of self-assembly from multiple mesojunction complexes have been overlooked in comparison to their counterparts based on regular junctions. In this work, we designed standardized component strands for the construction of complex mesojunction lattices. Three typical mesojunction configurations with three and four arms were showcased in the self-assembly of 1-, 2-, and 3-dimensional lattices constructed from both a scaffold-free tiling approach and a scaffolded origami approach.

Structure, Mechanical, and Micro-Scratch Behavior of Ta-Hf-C Solid Solution Coating Deposited by Non-Reactive Magnetron Sputtering.

The TaC, HfC, and Hf-Ta-C coatings are successfully prepared by non-reactively DC magnetron sputtering. The effects of working pressure and deposition temperature on the structure and mechanical properties of Ta-Hf-C coating are analyzed. The scratch performance of the Ta-Hf-C coating deposited on 304 stainless steel and tungsten substrates are investigated. Results show the hardness and elastic modulus of Ta-Hf-C solid solution coating both increase to 37.8 ± 1.1 GPa and 435.8 ± 13.8 GPa due to the solid solution strengthening effect. Plastic deformation resistance H3/E2 of Ta-Hf-C coating can reach 0.285, which is more than twice that of binary coating. Furthermore, the scratch performance and failure mechanism show that Ta-Hf-C coating has a weaker plastic deformation resistance on soft substrate and low friction characteristic (0.01) on hard substrate, which implies that Ta-Hf-C coating is a good protective coating that can be applied to cutting tools.

The Environmental Story During the COVID-19 Lockdown: How Human Activities Affect PM2.5 Concentration in China?

At the end of 2019, the very first COVID-19 coronavirus infection was reported and then it spread across the world just like wildfires. From late January to March 2020, most cities and villages in China were locked down, and consequently, human activities decreased dramatically. This letter presents an "offline learning and online inference" approach to explore the variation of PM2.5 pollution during this period. In the experiments, a deep regression model was trained to establish the complex relationship between remote sensing data and in situ PM2.5 observations, and then the spatially continuous monthly PM2.5 distribution map was simulated using the Google Earth Engine platform. The results reveal that the COVID-19 lockdown truly decreased the PM2.5 pollution with certain hysteresis and the fine particle pollution begins to increase when advancing resumption of work and production gradually.

[Retrospective and cost-effective analysis of the result of Changsha Municipal Public Welfare Program by Noninvasive Prenatal Testing].

OBJECTIVE: To assess the practical and health economical values of non-invasive prenatal test (NIPT) in Changsha Municipal Public Welfare Program. METHODS: A retrospective analysis was carried out on 149 165 women undergoing NIPT test from April 9, 2018 to December 31, 2019. For pregnant women with high risks, invasive prenatal diagnosis and follow-up of pregnancy outcome were conducted. The cost-benefit of NIPT for Down syndrome was analyzed. RESULTS: NIPT was carried out for 149 165 pregnant women and succeeded in 148 749 cases (99.72%), for which outcome were available in 148 538 (99.86%). 90% of pregnant women from the region accepted the screening with NIPT. 415 (0.27%) were diagnosed as high risk. Among these, 381 (91.81%) accepted amniocentesis, which led to the diagnosis of 212 cases of trisomy 21 (PPV=85.14%), 41 cases with trisomy 18 (PPV=48.81%) and 10 cases with trisomy 13 (PPV=20.83%). The sensitivity and specificity of NIPT for trisomy 21, trisomy 18 and trisomy 13 were (97.70%, 99.98%), (97.62%, 9.97%) and (100%, 99.97%), respectively. In addition, 213 and 30 cases were diagnosed with sex chromosomal aneuploidies (PPV=46.2%) and other autosomal anomalies (PPV=16.57%), respectively. For Down syndrome screening, the cost and benefit of the project was 120.79 million yuan and 1,056.95 million yuan, respectively. The cost-benefit ratio was 1: 8.75, and safety index was 0.0035. CONCLUSION: NIPT is a highly accurate screening test for trisomy 21, which was followed by trisomy 18 and sex chromosomal aneuploidies, while it was less accurate for other autosomal aneuploidies. The application of NIPT screening has a high health economical value.

Manipulation of Skyrmion Motion Dynamics for Logical Device Application Mediated by Inhomogeneous Magnetic Anisotropy.

Magnetic skyrmions are promising potential information carriers for future spintronic devices owing to their nanoscale size, non-volatility and high mobility. In this work, we demonstrate the controlled manipulation of skyrmion motion and its implementation in a new concept of racetrack logical device by introducing an inhomogeneous perpendicular magnetic anisotropy (PMA) via micromagnetic simulation. Here, the inhomogeneous PMA can be introduced by a capping nano-island that serves as a tunable potential barriers/well which can effectively modulate the size and shape of isolated skyrmion. Using the inhomogeneous PMA in skyrmion-based racetrack enables the manipulation of skyrmion motion behaviors, for instance, blocking, trapping or allowing passing the injected skyrmion. In addition, the skyrmion trapping operation can be further exploited in developing special designed racetrack devices with logic AND and NOT, wherein a set of logic AND operations can be realized via skyrmion-skyrmion repulsion between two skyrmions. These results indicate an effective method for tailoring the skyrmion structures and motion behaviors by using inhomogeneous PMA, which further provide a new pathway to all-electric skyrmion-based memory and logic devices.

[Protective effect of oleanolic acid liposomes on cisplatin-induced oligoasthenospermia in mice].

OBJECTIVE: To study the protective effect of oleanolic acid liposomes (OA-Lips) on cisplatin-induced oligoasthenospermia (COAS) in mice. METHODS: Sixty ICR mice were randomly divided into a normal control, a COAS model control, a positive control and a low-, a medium- and a high-dose OA-Lips group. The animals in the low-, medium- and high-dose OA-Lips and positive control groups were given intragastrically OA-Lips solution at 25, 50, and 100 mg/kg/d and vitamin E at 50 mg/kg/d, respectively. On the 28th day, the mice in the COAS model control, positive control and OA-Lips groups were injected intraperitoneally with cisplatin solution at 10 mg/kg, while those in the normal control group with the same dose of normal saline. Three days after administration, all the mice were sacrificed and their testis tissues collected for detection of the semen parameters and observation of the testicular morphology. RESULTS: Both the percentage of motile sperm and sperm concentration were significantly increased in the high-dose OA-Lips group (P < 0.05). HE staining showed that OA-Lips remarkably improved the damaged testis tissue (P < 0.05) and protected the seminiferous tubules and interstitial cells. The percentage of progressively motile sperm (PMS) and the curvilinear velocity (VCL), straight line velocity (VSL), average path velocity (VAP), linearity (LIN), straightness (STR), wobble (WOB), amplitude of lateral head displacement (ALH) and beat-cross frequency (BCF) of sperm were gradually increased in a dose-dependent manner in the OA-Lips groups. The serum T level was significantly higher (P < 0.05) in the OA-Lips-treated mice than in the COAS model controls while the percentage of morphologically abnormal sperm (MAS) markedly lower in the high-dose OA-Lips group than in the model control, positive control and low-dose OA-Lips groups (P < 0.05). CONCLUSION: OA-Lips can relieve oligoaspermia and improve the productive ability of mice.

Kinesin-binding protein remodels the kinesin motor to prevent microtubule binding.

Kinesins are regulated in space and time to ensure activation only in the presence of cargo. Kinesin-binding protein (KIFBP), which is mutated in Goldberg-Shprintzen syndrome, binds to and inhibits the catalytic motor heads of 8 of 45 kinesin superfamily members, but the mechanism remains poorly defined. Here, we used cryo­electron microscopy and cross-linking mass spectrometry to determine high-resolution structures of KIFBP alone and in complex with two mitotic kinesins, revealing structural remodeling of kinesin by KIFBP. We find that KIFBP remodels kinesin motors and blocks microtubule binding (i) via allosteric changes to kinesin and (ii) by sterically blocking access to the microtubule. We identified two regions of KIFBP necessary for kinesin binding and cellular regulation during mitosis. Together, this work further elucidates the molecular mechanism of KIFBP-mediated kinesin inhibition and supports a model in which structural rearrangement of kinesin motor domains by KIFBP abrogates motor protein activity.

Sediment metals adhering to biochar enhanced phosphorus adsorption in sediment capping.

Metal ions in sediment are inherent Ca and Fe sources for biochar modification. In this work, the effect of Ca2+ and Fe2+ released from sediment on biochar for phosphorus adsorption was evaluated. Results showed that raw peanut shell biochar (PSB) was poor in phosphorus adsorption (0.48 mg/g); sediment-triggered biochar (S-PSB) exhibited a P adsorption capacity of 1.32 mg/g in capping reactor and maximum adsorption capacity of 10.72 mg/g in the Langmuir model. Sediment released Ca2+ of 2.2-4.1 mg/L and Fe2+/Fe3+ of 0.2-9.0 mg/L. The metals loaded onto the biochar surface in the forms of Ca-O and Fe-O, with Ca and Fe content of 1.47 and 0.29%, respectively. Sediment metals made point of zero charge (pHpzc) of biochar shifted from 5.39 to 6.46. The mechanisms of enhanced P adsorption by S-PSB were surface complexation of CaHPO4 followed by precipitation of Ca3(PO4)2 and Ca5(PO4)3(OH). Sediment metals induced the modification of biochar and improvement of P adsorption, which was feasible to overcome the shortcomings of biochar on phosphorus control in sediment capping.

Effects of acupuncture on Luteinized Unruptured Follicle Syndrome: A meta-analysis of randomized controlled trials.

PURPOSE: This meta-analysis aimed to evaluate the comprehensive efficiency and safety of acupuncture on Luteinized Unruptured Follicle Syndrome based on Randomized Controlled Trials (RCTs). METHODS: Six electronic databases (i.e. Wanfang, VIP, China National Knowledge Infrastructure, Pubmed, Cochrane, and Embase) were searched from inception to July 2019. Randomized controlled trials were eligible to evaluate the effects of acupuncture alone or acupuncture as an adjunct. The primary outcomes were the ovulation rate and pregnancy rate. Two reviewers proceeded study selection and quality assessment of included trials and performed heterogeneity of included studies before meta-analysis.Trial Sequential Analysis was used to assess the risk of random error and estimate required information size. The Grading of Recommendations Assessment, Development and Evaluation was applied for assessing level of evidence. RESULTS: 10 studies involving 715 participants were included Meta-analysis showed acupuncture alone and acupuncture as an adjunct both could significantly improve ovulation, which were confirmed by Trial Sequential Analysis. The evidence of acupuncture improving pregnancy rate was insufficient. Improved serum luteinizing hormone and estradiol levels, and decreased pulsatility index and resistance index of ovary artery were shown in both two subgroups. Level of evidence of most outcomes was "low" or "very low", so the results should be cautiously interpreted. CONCLUSIONS: Acupuncture alone or be combined with drugs are effective on Luteinized Unruptured Follicle Syndrome especially for improving ovulation . While concurrent evidence is insufficient, and further studies of high quality are needed to strengthen the conclusion.

Miro: A molecular switch at the center of mitochondrial regulation.

The orchestration of mitochondria within the cell represents a critical aspect of cell biology. At the center of this process is the outer mitochondrial membrane protein, Miro. Miro coordinates diverse cellular processes by regulating connections between organelles and the cytoskeleton that range from mediating contacts between the endoplasmic reticulum and mitochondria to the regulation of both actin and microtubule motor proteins. Recently, a number of cell biological, biochemical, and protein structure studies have helped to characterize the myriad roles played by Miro. In addition to answering questions regarding Miro's function, these studies have opened the door to new avenues in the study of Miro in the cell. This review will focus on summarizing recent findings for Miro's structure, function, and activity while highlighting key questions that remain unanswered.

IL-36 s in the colorectal cancer: is interleukin 36 good or bad for the development of colorectal cancer?

BACKGROUND AND AIMS: Colorectal cancer (CRC) is a major killer. Host immunity is important in tumorigenesis. Direct comparison among IL-36α, IL-36ß and IL-36γ in the prognosis of CRC is unclear. METHODS: CRC tissue arrays were generated from colorectostomy samples with TNM stage, invasion depth and the demography of these patients (n = 185). Using immunohistochemistry/histopathology, IL-36α, IL-36ß and IL-36γ were determined, in comparison to non-cancer tissues. RESULTS: A significant association was observed between colonic IL-36α, IL-36ß or IL-36γ and the presence of cancer (with all P < 0.0001). Using ROC curve analysis, specificity and sensitivity of IL-36α, IL-36ß or IL-36γ were confirmed, with area under the curve (AUC) values of 0.68, 0.73 and 0.65, respectively. Significant differences in survival were observed between IL-36αhigh and IL-36αlow (P = 0.003) or IL-36γhigh and IL-36γlow (P = 0.03). Survival curves varied significantly when further stratification into sub-groups, on the basis of combined levels of expression of two isotypes of IL-36 was undertaken. A significant difference was observed when levels of IL-36α and IL-36ß were combined (P = 0.01), or a combination of IL-36α plus IL-36γ (P = 0.002). The sub-groups with a combination of IL-36αhigh plus IL-36ßhigh, or IL-36αhigh plus IL-36γlow exhibited the longest survival time among CRC patients. In contrast, the sub-groups of IL-36αlow plus IL-36ßhigh or IL-36αlow plus IL-36γhigh had the shortest overall survival. Using the log-rank test, IL-36αhigh expression significantly improved survival in patients with an invasion depth of T4 (P < 0.0001), lymph node metastasis (P = 0.04), TNM III-IV (P = 0.03) or with a right-sided colon tumour (P = 0.02). Similarly, IL-36γlow expression was significantly associated with improved survival in patients with no lymph node metastasis (P = 0.008), TNM I-II (P = 0.03) or with a left-sided colon tumour (P = 0.05). Multivariate analysis demonstrated that among IL-36α, IL-36ß and IL-36γ, only IL-36α (HR, 0.37; 95% CI, 0.16-0.87; P = 0.02) was an independent factor in survival, using Cox proportional hazards regression analysis. CONCLUSION: IL-36α or IL-36γ are reliable biomarkers in predicting the prognosis of CRC during the later or early stages of the disease, respectively. Combining IL-36α plus IL-36γ appears to more accurately predict the postoperative prognosis of CRC patients. Our data may be useful in the management of CRC.

Interleukin-38 in colorectal cancer: a potential role in precision medicine.

Colorectal cancer (CRC) is a leading cause of cancer-related death, partly due to a lack of reliable biomarkers for early diagnosis. To improve the outcome of CRC, it is critical to provide diagnosis at an early stage using promising sensitive/specific marker(s). Using immunohistochemistry and histopathology, IL-38 expression was determined in tissue arrays of CRC with different TNM status and depth of tumour invasion. Data were compared to IL-38 in adjacent non-cancer tissue and correlated with demographic information, including survival. A substantial reduction of IL-38 was detected in the CRC tissue compared to adjacent non-cancer colonic tissue. IL-38 correlated with the extent of tumour differentiation (P < 0.0001); CRC location in the left side of the colon (P < 0.05), and smaller tumour size (≤ 5 cm; P < 0.05). Receiver operating characteristic (ROC) curve analysis demonstrated both high specificity and high sensitivity of IL-38 for the diagnosis of CRC [area under the curve (AUC) = 0.89)]. By sub-group analysis, AUC of IL-38 for the diagnosis of CRC was higher in poorly differentiated, right-sided CRC or tumour size > 5 cm (all AUC > 0.9). Significantly, longer survival was observed for the IL-38high versus the IL-38low groups in CRC patients (P = 0.04). Survival was also longer for IL-38high patients with lymph node metastasis (P = 0.01) and TNM stage III-IV (P = 0.02). Multivariate analysis demonstrated that IL-38 (P = 0.05) and tumour invasion depth (P = 0.04) were independent factors for survival. High IL38 in CRC is an independent prognostic factor for the longer survival of CRC patients. IL-38 signalling may constitute a therapeutic target in CRC.

Self-Assembly of Wireframe DNA Nanostructures from Junction Motifs.

Wireframe frameworks have been investigated for the construction of complex nanostructures from a scaffolded DNA origami approach; however, a similar framework is yet to be fully explored in a scaffold-free "LEGO" approach. Herein, we describe a general design scheme to construct wireframe DNA nanostructures entirely from short synthetic strands. A typical edge of the resulting structures in this study is composed of two parallel duplexes with crossovers on both ends, and three, four, or five edges radiate out from a certain vertex. By using such a self-assembly scheme, we produced planar lattices and polyhedral objects.

Investigation on the correlation between energy deposition and clustered DNA damage induced by low-energy electrons.

This study presents the correlation between energy deposition and clustered DNA damage, based on a Monte Carlo simulation of the spectrum of direct DNA damage induced by low-energy electrons including the dissociative electron attachment. Clustered DNA damage is classified as simple and complex in terms of the combination of single-strand breaks (SSBs) or double-strand breaks (DSBs) and adjacent base damage (BD). The results show that the energy depositions associated with about 90% of total clustered DNA damage are below 150 eV. The simple clustered DNA damage, which is constituted of the combination of SSBs and adjacent BD, is dominant, accounting for 90% of all clustered DNA damage, and the spectra of the energy depositions correlating with them are similar for different primary energies. One type of simple clustered DNA damage is the combination of a SSB and 1-5 BD, which is denoted as SSB + BD. The average contribution of SSB + BD to total simple clustered DNA damage reaches up to about 84% for the considered primary energies. In all forms of SSB + BD, the SSB + BD including only one base damage is dominant (above 80%). In addition, for the considered primary energies, there is no obvious difference between the average energy depositions for a fixed complexity of SSB + BD determined by the number of base damage, but average energy depositions increase with the complexity of SSB + BD. In the complex clustered DNA damage constituted by the combination of DSBs and BD around them, a relatively simple type is a DSB combining adjacent BD, marked as DSB + BD, and it is of substantial contribution (on average up to about 82%). The spectrum of DSB + BD is given mainly by the DSB in combination with different numbers of base damage, from 1 to 5. For the considered primary energies, the DSB combined with only one base damage contributes about 83% of total DSB + BD, and the average energy deposition is about 106 eV. However, the energy deposition increases with the complexity of clustered DNA damage, and therefore, the clustered DNA damage with high complexity still needs to be considered in the study of radiation biological effects, in spite of their small contributions to all clustered DNA damage.