Effects of biodegradable microplastics on arsenic migration and transformation in paddy soils: a comparative analysis with conventional microplastics.

The combined pollution of microplastics (MPs) and arsenic (As) in paddy soils has attracted more attention worldwide. However, there are few comparative studies on the effects of biodegradable and conventional MPs on As migration and transformation. Therefore, conventional (polystyrene, polyethylene, polyvinyl chloride) and biodegradable (polybutadiene styrene, polylactic acid, polybutylene adipate terephthalate) MPs were selected to explore and demonstrate their influences and mechanism on As migration from paddy soils to overlying water and As speciation transformation through microcosmic experiment with measuring the changes of As chemical distribution, physicochemical indexes and microbial community in paddy soils. The results showed that biodegradable MPs enhanced As migration and transformation more effective than conventional MPs during 60 d. Biodegradable MPs indirectly increased the content of As(Ⅲ) and bioavailable As by changing the microbial community structure and affecting the biogeochemical cycles of carbon, nitrogen, sulfur and iron in soils, and promoted the As migration and transformation. PBS showed the strongest promoting effect, transforming to more As(Ⅲ) (11.43%) and bioavailable As (4.28%) than control. This helps to a better understanding of the effects of MPs on As biogeochemical cycle and to clarify the ecological and food safety risks of their combined pollution in soils.

Influence of landform, soil properties, soil Cd pollution and rainfall on the spatial variation of Cd in rice: Contribution and pathway models based on big data.

Landform, soil properties, soil cadmium (Cd) pollution and rainfall are the important factors affecting the spatial variation of rice Cd. In this study, we conducted big data mining and model analysis of 150,000 rice-soil sampling sites to examine the effects by the above four factors on the spatial variation of rice Cd in Hunan Province, China. Specifically, the variable coefficient of rice Cd in space was significantly correlated with the partition scale according to the logistic fitting. The improved random forest results suggested that elevation (DEM) and pH were the two most important factors affecting the spatial variation of rice Cd, followed by relief, soil Cd content and rainfall. Typically, variance partitioning analysis (VPA) revealed that both the soil property and the interactive effects between the soil property and Cd pollution were the principal contributors to the rice-Cd variation, with the respective contributing rates of 30.5 % and 29.0 %. Meanwhile, the partial least square-structural equation modelling (PLS-SEM) elucidated 4 main paths of specific indirect effects on rice-Cd variation. They were landform → physicochemical property → soil acidity → rice-Cd variation, landform → soil acidity → rice-Cd variation, physicochemical property → soil acidity → rice-Cd variation, and soil texture → soil acidity → rice-Cd variation. This work can provide a general guidance for scientific zoning, accurate prediction and prevention of Cd pollution in paddy fields.

HOXC Cluster Antisense RNA 3, a Novel Long Non-Coding RNA as an Oncological Biomarker and Therapeutic Target in Human Malignancies.

HOXC cluster antisense RNA 3 (HOXC-AS3) is a novel long noncoding RNA (lncRNA) that exhibits aberrant expression patterns in various cancer types. Its expression is closely related to clinicopathological features, demonstrating significant clinical relevance across multiple tumors. And HOXC-AS3 plays multifaceted roles in tumor progression, impacting cell proliferation, apoptosis, migration, invasion, epithelial-mesenchymal transition (EMT), autophagy, senescence, tumor growth, and metastasis. In this review, we summarized and comprehensively analyzed the expression and clinical significance of HOXC-AS3 as a diagnostic and prognostic biomarker for malignancies. Additionally, we presented an in-depth update on HOXC-AS3's functions and regulatory mechanisms in cancer pathogenesis. This narrative review underscores the importance of HOXC-AS3 as a promising lncRNA candidate in cancer research and its potential as a predictive biomarker and therapeutic target in clinical applications.

[Effects of Equal Amounts Silicon Fertilizer Application on Soil Bioavailability of Cadmium and Cadmium Uptake by Rice].

Cadmium (Cd) contamination of paddy fields is a global concern, as it can cause the accumulation of Cd in food. To explore the effects of equal application of silicon fertilizers on the bioavailability of cadmium and soil Cd uptake at different growth stages of rice, a field experiment was conducted with five silicon fertilizers under the same silicon dose (225 kg·hm-2). The results revealed that the Cd contents in roots, stems, and leaves increased with the extension of the rice growth stage. The application of silicon fertilizers reduced the Cd contents in roots, stems, and leaves in brown rice by 14.9%, 28.2%, and 12.2%, respectively. Compared with that in the control, the Cd content of brown rice in the SiCaMgFe and SiW treatments was decreased by 21.1% (P<0.05) and 21.2% (P<0.05), respectively. Similarly, Cd content in iron plaque (DCB-Cd) increased with the extension of the rice growth period, which accounted for 15.8%-42.8% of the total Cd content in roots, and the DCB-Cd content was different in each stage of rice. The content of exchangeable Cd (Exc-Cd) in soil at the mature stage of rice decreased by 36.4%, and the other fractions increased by 12.5%-48.2%. The results showed significant negative correlations between the Cd contents and Si in roots, DCB-Cd and soil available Cd and available Si, Exc-Cd and Car-Cd, and soil available Cd and pH value. Cd content in roots was positively correlated with DCB-Cd. With the equal dose of silicon fertilizer, the treatments of SiCaMgFe and SiW could effectively reduce the Cd content in rice. The application of silicon fertilizer promoted the transfer of Exc-Cd to Carb-Cd by increasing the soil pH value and the soil available Si content, meanwhile reducing the soil available Cd, Exc-Cd contents, the adsorption of Cd by the iron film on the root surface, and the adsorption capacity of iron plaque and root, thereby reducing the absorption of Cd by rice.

Enhanced As extraction from paddy soils with high As contamination risk by rice plant upon Si fertilization.

Owing to flooded growing conditions and specific physiological characteristics, rice plant is more efficient in As uptake and accumulation, which provides a cost-effective and time-efficient pathway to deplete bioavailable As from paddy soils. In the present study, the enhancing effect of silicon (Si) fertilization on As extraction from heavily contaminated paddy soils by rice was explored Upon incorporation of one weak acid Si fertilizer (AcSF), soil As solubility was significantly promoted by 1.3-1.4-fold, while a slightly increase in porewater As was observed with alkaline soluble Si fertilizer Na2SiO3 (AlSF). With both Si fertilizers applied before transplanting, a relatively low Si/As molar ratio (<100) in soil porewater was obtained, As a result, soil As uptake by rice plant with Si fertilizers was enhanced by 37.2%-171.7% compared to control (CK). Notably, up to 91.6% of the total As in rice plant retained in root with Si fertilization, suggesting the importance of root removal. By harvesting the whole rice plant including roots, soil bioavailable As measured by diffusive gradients in thin films (DGT) declined by 26.9%-31.3% in AlSF treatments relative to CK. Total soil As depletion by the whole rice plant was significantly enhanced from 2.8% in CK to 7.0%-11.2% in Si fertilizer treatments. In this way, 197.5 mg As m-2-232.5 mg As m-2 could be eliminated from soil following one rice-growth season, which was 2.3-2.7-fold higher compared to CK. These results identified the effectiveness of soluble Si fertilizer in enhancing soil As depletion by rice from paddy soils with high As contamination risk, which could serve as a cost-effective strategy with little technical-restriction.

Silicon facilitated the physical barrier and adsorption of cadmium of iron plaque by changing the biochemical composition to reduce cadmium absorption of rice roots.

Silicon effectively inhibits cadmium (Cd) uptake in rice, iron plaque on root surface was the primary link and first interface of Cd entering into rice root. To elucidate the mechanism of iron plaque under silicon treatment on root Cd uptake, the morphological characteristics of iron plaque, mechanisms of Cd adsorption of iron plaque and effect of iron plaque on Cd uptake by rice roots of Yuzhenxiang (YZX) and Xiangwanxian (XWX) rice varieties were studied by employing energy spectrum analysis technique, non-invasive micro-test technique, and isothermal-kinetic adsorption method. Scanning electron microscopy-X-ray energy dispersive (SEM-EDX) analysis showed that denser crystal structure of iron plaque was observed at Si treatment, silicon promoted the thickening of iron plaque and strengthened the isolation of iron plaque to Cd, which reduced the Cd content of white roots of YZX and XWX varieties by 30.2% and 20.9% respectively. However, the blocking effect of iron plaque on Cd was weakened under silicon treatment with iron plaque removed, Cd content in iron plaque of YZX and XWX cultivars was significantly decreased by 36.3% and 18.4%, Cd concentrations in white root and shoot was significantly increased, and the influxes of Cd2+ at elongation and maturation zone of root were increased in multiples. The results of adsorption test showed that the adsorption process of iron plaque was mainly a monolayer adsorption completed by boundary diffusion. The X-ray photoelectron spectroscopy (XPS) results demonstrated that silicon changed the biochemical composition of iron plaque and increased the density of the carbon-oxygen bound groups on iron plaque, which is the most likely reasons for the higher affinity of Cd adsorption ability of iron plaque observed in the silicon treated iron plaque. This study suggested the silicon-facilitated iron plaque have played critical effects in controlling the Cd accumulation in rice roots by changing the morphology and chemical composition of iron plaque.

Remediation of Cd contaminated paddy fields by intercropping of the high- and low- Cd-accumulating rice cultivars.

Intercropping cadmium (Cd) hyperaccumulators with crops have been widely applied in the remediation of contaminated farmland soils. However, most studies were done on drylands since the majority of the hyperaccumulators are susceptible to the aquatic environment, making the remediation of Cd-contaminated paddy fields particularly difficult. Our study attempts to address the issue by intercropping the high-Cd-accumulating (henceforth, "high-Cd") rice cultivars with the low-Cd-accumulating (henceforth, "low-Cd") ones, and to study the Cd removal, uptake and translocation during the remediation process. The results indicated that intercropping mode with 20-cm row spacing (intercropping-20 treatment) performed better than the that with 30-cm row spacing (intercropping-30 treatment), while intercropping had stronger impact on late rice compared to early rice. In general, the physiological condition of rice was stable under the intercropping-20 treatment, suggesting the growth of rice was not impeded. For late rice, as the intercropping-20 treatment can significantly reduce soil pH and increase the diethylenetriaminepentaacetic acid extracted Cd (DTPA-extracted Cd) from the rhizosphere soil, Cd accumulated more in the tissues of the high-Cd rice cultivars (H2), and its dry biomass increased. As a result, a drastic improvement in the total Cd removal rate by 38.55 % was noticed. Therefore, the reduction of total Cd concentration in 0-20 cm profile caused by removal, thus it could provide safer soil environment for the growth of low Cd-rice cultivars (L2), leading to a significant drop in the root Cd concentration and safer production of L2. Interestingly, intercropping had no effect on the yield per plant of low-Cd rice cultivars. For early rice, intercropping-20 treatment exerted trivial effects to all aspects. The intercropping-30 treatment has poor representativeness of all indicators because of the large intercropping distance. Our results demonstrate that intercropping of the high-Cd and the low-Cd rice cultivars is a potential mode for Cd remediation in paddy fields.

[Primary Factors Affecting Soil Bioavailable Cadmium and Asenic by Different Properties of Silicon Fertilizer].

To clarify the primary factors affecting soil bioavailable cadmium (Cd) and arsenic (As) by silicon fertilizer, we chose different properties of silicon fertilizer, including three types of alkaline silicon fertilizer[Na2SiO3, CaSiO3, and ASSF (pH 9-11)] and one weak acid neutral soluble silicon fertilizer (NSSF, pH 5-6), to carry out a pot experiment by adding different amounts of Si fertilizer (25-800 mg·kg-1, calculated as Si). After 21 days of flooding, soil basic physical and chemical properties, along with diffusive gradients in thin film Cd and As (DGT-Cd and DGT-As) were investigated. The results showed that the application of Si fertilizer with different properties had different significant effects on the basic physical and chemical properties of soil. Specifically, the three types of alkaline silicon fertilizer significantly increased the soil pH (P<0.05), among which Na2SiO3 exhibited the strongest ability; however, the application of NSSF remarkably reduced soil pH (P<0.05), and per unit (mg) Si application of NSSF could reduce soil pH by 0.0017 units. Furthermore, with each fertilizer application rate that reached 400 mg·kg-1 (calculated as Si), the changes in soil pH and Eh tended to be gentle. The ability of the four types of silicon fertilizer to improve soil available silicon ranked as NSSF>Na2SiO3>ASSF>CaSiO3. Additionally, the application of the three types of alkaline silicon fertilizer apparently decreased soil DGT-Cd while increasing soil DGT-As (P<0.05). When the addition rate of CaSiO3 was up to 100 mg·kg-1(calculated as Si), soil DGT-Cd concentration could be significantly decreased by approximately 50.89% without causing a significant increase in soil DGT-As concentration. Conversely, when the NSSF application rate was up to 400 mg·kg-1 (calculated as Si), the soil DGT-As basically reached its steady-state, and the DGT-As reduction rate reached 85.87%. Strikingly, the correlation analysis of the influencing factors of soil DGT-Cd and DGT-As showed that soil pH was the main factor affecting soil bioavailable Cd and As (DGT-Cd and DGT-As), and the effect of soil available Si and P on soil Cd and As bioavailability was negligible. Consequently, soil DGT-Cd and soil DGT-As could reach a minimum when soil pH was adjusted to 6.5-7.0 or 5-5.5 by alkaline silicon fertilizer or NSSF, respectively. It is undoubtedly of great significance, to clarify the primary factors that influence soil bioavailable Cd and As to ensure food security production.

Insights into Pyrroloquinoline Quinone (PQQ) Effects on Soil Nutrients and Pathogens from Pepper Monocropping Soil under Anaerobic and Aerobic Conditions.

Imbalances of soil available nutrients and soilborne diseases have seriously restricted the productivity of crops and jeopardized food security worldwide. Pyrroloquinoline quinone (PQQ), a redox cofactor in some bacteria involved in glucose metabolism and phosphorus mineralization, could be anticipated to alter soil ecosystems to a certain extent. However, there is limited information on PQQ defending soilborne pathogens and regulating soil main nutrients. Here, a pot experiment based on mono-cropping soils of pepper was conducted to examine the effects of PQQ amendment on reconstructing soil microbial communities and soil nutrients under aerobic/anaerobic conditions comprising three treatments, namely, control, PQQ (aerobic), and FL-PQQ (anaerobic). The results revealed that soil microbial community composition and soil nutrients were distinctly altered by PQQ regimes. Compared to control, PQQ treatment significantly increased the content of soil available phosphorus (AP), while FL_PQQ treatment strongly improved the content of soil available nitrogen (AN). In terms of pathogens, relative to control, both PQQ treatments suppressed the abundances of pathogens, of which FL_PQQ treatment significantly decreased the abundance of the pathotrophic fungal by 64% and the abundance of Fusarium oxysporum by 57%, largely attributed to the increase of organic acid generators (Oxobacter, Hydrogenispora) and potential antagonists (Bacillus, Talaromyces). Structural equation modeling (SEM) showed that PQQ regimes suppressed pathogens by indirectly regulating soil physicochemical properties and microbial communities. Overall, we proposed that PQQ application both in aerobic/anaerobic conditions could improve soil available nutrients and suppress soil pathogens in pepper monocropping soils. IMPORTANCE The attention to PQQ (pyrroloquinoline quinone) effect on soil nutrients and pathogens was less paid in monocropping soils. However, the underlying microbial interacting mechanism remains unclear. Adopting a novel external bio-additive, the effects of PQQ on soil main nutrients and the pathotrophic fungal under aerobic and anaerobic regimes will be investigated, which would help to improve soil quality health. Our main conclusion was that PQQ would help to remediate monocropping obstacle soils in terms of soil nutrients and soil pathogens by associating with the microbial community, and anaerobic PQQ application more favored amelioration of continuous obstacle soils. These results will benefit the health and sustainable development of pepper production as well as other greenhouse vegetable production.

Effects of Cd uptake, translocation and redistribution in different hybrid rice varieties on grain Cd concentration.

In order to identify the key transport process that determines the Cd concentration in brown rice, this study used 21 hybrid rice varieties as experimental materials and conducted field experiments in Qiyang (cadmium-contaminated site) and Yongding (low-cadmium site). Cd concentrations in 8 organs were measured, and bioconcentration factors and transfer factor were further calculated. The results showed that the Cd concentrations of the organs related to the xylem transport were as follows: root > node > stem > leaf sheath > leaf. In the phloem, the Cd concentrations were as follows: rachis > brown rice > rice husk. And the results of the correlation analysis found that Cd concentration between brown rice and root showed a significant positive correlation in Cd-contaminated site, but no significant correlation in low-cadmium site. Meanwhile, at both experimental sites, the Cd concentration of brown rice showed the most significant correlation with the phloem transfer factor from leaf and leaf sheath to brown rice. Principal Component Analysis (PCA) and stepwise regression analysis likewise found that Cd concentration in leaf and leaf sheath and their phloem transport of Cd to brown rice were significantly and positively correlated with Cd concentration in brown rice. The above results showed that the transport of leaf and leaf sheath to brown rice was a key process, and played a more important role in the accumulation of cadmium in brown rice than in root.

Influence of soil properties on cadmium accumulation in vegetables: Thresholds, prediction and pathway models based on big data.

Soil properties, such as soil pH, soil organic matter (SOM), cation exchange capacity (CEC), are the most important factors affecting cadmium (Cd) accumulation in vegetables. In this study, we conducted big data mining of 31,342 soil and vegetable samples to examine the influence of soil properties (soil pH, SOM, CEC, Zn and Mn content) on the accumulation of Cd in root, solanaceous, and leafy vegetables in Hunan Province, China. Specifically, the Cd accumulation capability was in the following order: leafy vegetables > root vegetables > solanaceous vegetables. The soil property thresholds for safety production in vegetables were determined by establishing nonlinear models between Cd bioaccumulation factor (BCF) and the individual soil property, and were 6.5 (pH), 30.0 g/kg (SOM), 13.0 cmol/kg (CEC), 100-140 mg/kg (Zn), and 300-400 mg/kg (Mn). When soil property values were higher than the thresholds, Cd accumulation in vegetables tended to be stable. Prediction models showed that pH and soil Zn were the leading factors influencing Cd accumulation in root vegetables, explaining 87% of the variance; pH, SOM, soil Zn and Mn explained 68% of the variance in solanaceous vegetables; pH and SOM were the main contributors in leafy vegetables, explaining 65% of the variance. Further, variance partitioning analysis (VPA) revealed that the interaction effect of the corresponding key soil properties contributed mostly to BCF. Meanwhile, partial least squares (PLS) path modeling was employed to analyze the path and the interactive effects of soil properties on Cd BCF. pH and SOM were found to be the biggest two players affecting BCF in PLS-models, and the most substantial interactive influence paths of soil properties on BCF were different among the three types of vegetables.

Combined amendment improves soil health and Brown rice quality in paddy soils moderately and highly Co-contaminated with Cd and As.

In situ remediation technology applied aims to not only decrease cadmium (Cd) and arsenic (As) uptake by rice but also improve soil health and rice quality in contaminated paddy soils. Here the effects of a combined amendment, consisting of limestone, iron powder, silicon fertilizer, and calcium-magnesium-phosphate fertilizer, with three application rates (0, 450, and 900 g m-2) on soil health, rice root system, and brown rice quality were compared in moderately versus highly Cd and As co-contaminated paddy fields. After the amendment application, soil pH, cation exchange capacity, four kinds of soil enzyme activities increased (sucrase, urease, acid phosphatase, and catalase), and concentrations of leached Cd/As decreased, as measured by the DTPA (diethylene triamine pentaacetic acid) and TCLP (toxicity characteristic leaching procedure). Changes in the above soil indicators promoted soil health. In both fields, the dithionite-citrate-bicarbonate (DCB)-Fe and DCB-Mn concentration in iron plaque increased and root length became longer. Changes in the above root system indicators reduced the root system's absorption of Cd and As but increased that of nutrients. Under 900 g m-2 treatment, the Cd concentration in brown rice of two sites decreased by 55.8% and 28.9%, likewise inorganic As (iAs) decreased by 50.0% and 21.1%, whereas essential amino acids increased by 20.4% and 20.0%, respectively. Furthermore, the Cd and iAs concentrations in brown rice were <0.2 mg kg-1 (maximum contaminant level of Cd and iAs in the Chinese National Food Safety Standards GB2762-2017 for brown rice) under the 900 g m-2 in the moderately contaminated field. These results suggest the combined amendment can improve soil health and brown rice quality in the moderately and highly Cd- and As-co-contaminated paddy soils, offering potential eco-friendly and efficient remediation material for applications in such polluted paddy soils.

The role of silicon in cadmium alleviation by rice root cell wall retention and vacuole compartmentalization under different durations of Cd exposure.

Silicon (Si) plays a pivotal role in mitigating phytotoxicity caused by cadmium (Cd). However, few former reports focused on the internal mechanism how Si assisted in alleviating Cd stress in rice under different durations of Cd exposure. Herein, the effects of Si on subcellular distribution of Cd in rice roots under short-term (12 h) and long-term (20 d) Cd exposure were explored. Results showed that Si decreased shoot Cd concentration but had little impact on root Cd levels. Under short-term Cd exposure, subcellular distribution analysis showed that Si increased the ratio of Cd in root cell wall by 23.2~24.0%, and decreased the ratio of Cd in root soluble fraction by 20.6~21.5%. This suggested that Si supply improved root retention of Cd by fixing it on the cell wall and thus restricted intracellular transportation of Cd. Further analysis unraveled that pectin (especially ionic-soluble pectin) of the cell wall was the main binding component, and Si supply induced more Cd accumulation in covalent-soluble pectin and hemicellulose. Moreover, the overexpression of germin-like proteins (GLPs) proved the role of cell wall in moderating Cd toxicity. Under long-term Cd exposure, Si promoted phytochelatin 2 (PC2) and phytochelatin 3 (PC3) synthesis in cytosol, at the same time, Si down-regulated the expression of the Cd efflux-related protein multidrug resistance-associated protein-like ATP-binding cassette transporters (MRP-like ABC transporters) and limited Cd transportation from vacuole to cytosol. Taken together, Si rather predominates in limiting Cd translocation by the cell wall of root under short-term Cd exposure and promoting vacuole compartmentalization to mitigate the Cd toxicity under long-term exposure, instead of reducing the absorption of Cd in rice roots, thereby decreasing Cd delivery into shoots.

Automated clinical target volume delineation using deep 3D neural networks in radiation therapy of Non-small Cell Lung Cancer.

BACKGROUND AND PURPOSE: Clinical targeted volume (CTV) delineation accounting for the patient-specific microscopic tumor spread can be a difficult step in defining the treatment volume. We developed an intelligent and automated CTV delineation system for locally advanced non-small cell lung carcinoma (NSCLC) to cover the microscopic tumor spread while avoiding organs-at-risk (OAR). MATERIALS AND METHODS: A 3D UNet with a customized loss function was used, which takes both the patients' respiration-correlated ("4D") CT scan and the physician contoured internal gross target volume (iGTV) as inputs, and outputs the CTV delineation. Among the 84 identified patients, 60 were randomly selected to train the network, and the remaining as testing. The model performance was evaluated and compared with cropped expansions using the shape similarities to the physicians' contours (the ground-truth) and the avoidance of critical OARs. RESULTS: On the testing datasets, all model-predicted CTV contours followed closely to the ground truth, and were acceptable by physicians. The average dice score was 0.86. Our model-generated contours demonstrated better agreement with the ground-truth than the cropped 5 mm/8 mm expansion method (median of median surface distance of 1.0 mm vs 1.9 mm/2.0 mm), with a small overlap volume with OARs (0.4 cm3 for the esophagus and 1.2 cm3 for the heart). CONCLUSIONS: The CTVs generated by our CTV delineation system agree with the physician's contours. This approach demonstrates the capability of intelligent volumetric expansions with the potential to be used in clinical practice.

Investigating beam range uncertainty in proton prostate treatment using pelvic-like biological phantoms.

This study aims to develop a method for verifying site-specific and/or beam path specific proton beam range, which could reduce range uncertainty margins and the associated treatment complications. It investigates the range uncertainties from both CT HU to relative stopping power conversion and patient positioning errors for prostate treatment using pelvic-like biological phantoms. Three 25 × 14 × 12 cm3phantoms, made of fresh animal tissues mimicking the pelvic anatomies of prostate patients, were scanned with a general electric CT simulator. A 22 cm circular passive scattering beam with 29 cm range and 8 cm modulation width was used to measure the water equivalent path lengths (WEPL) through the phantoms at multiple points using the dose extinction method with a MatriXXPT detector. The measured WEPLs were compared to those predicted by TOPAS simulations and ray-tracing WEPL calculations. For the three phantoms, the WEPL differences between measured and theoretical prediction (WDMT) are below 1.8% for TOPAS, and 2.5% for ray-tracing. WDMT varies with phantom anatomies by about 0.5% for both TOPAS and ray-tracing. WDMT also correlates with the tissue types of a specific treated region. For the regions where the proton beam path is parallel to sharp bone edges, the WDMTs of TOPAS and ray-tracing respectively reach up to 1.8% and 2.5%. For the region where proton beams pass through just soft tissues, the WDMT is mostly less than 1% for both TOPAS and ray-tracing. For prostate treatments, range uncertainty depends on the tissue types within a specific treated region, patient anatomies and the range calculation methods in the planning algorithms. Our study indicates range uncertainty is less than 2.5% for the whole treated region with both ray-tracing and TOPAS, which suggests the potential to reduce the current 3.5% range uncertainty margin used in the clinics by at least 1% even for single-energy CT data.

Toward Personalized Radiation Therapy of Liver Metastasis: Importance of Serial Blood Biomarkers.

PURPOSE: To assess the added value of serial blood biomarkers in liver metastasis stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS: Eighty-nine patients were retrospectively included. Pre- and midtreatment blood samples were analyzed for potential biomarkers of the treatment response. Three biomarker classes were studied: gene mutation status, complete blood count, and inflammatory cytokine concentration in plasma. One-year local failure (LF) and 2-year overall survival (OS) were chosen as study end points. Multivariate logistic regression was used for response prediction. Added predictive benefit was assessed by quantifying the difference between the predictive performance of a baseline model (clinicopathologic and dosimetric predictors) and that of the biomarker-enhanced model, using three metrics: (1) likelihood ratio, (2) predictive variance, and (3) area under the receiver operating characteristic curve (AUC). RESULTS: The most important predictors of LF were mutation in KRAS gene (hazard ratio [HR] = 2.92, 95% CI, [1.17 to 7.28], P = .02) and baseline and midtreatment concentration of plasma interleukin-6 (HR = 1.15 [1.04 to 1.26] and 1.06 [1.01 to 1.13], P = .01). Absolute lymphocyte count and platelet-to-lymphocyte ratio at baseline as well as neutrophil-to-lymphocyte ratio at baseline and before fraction 3 (HR = 1.33 [1.16 to 1.51] and 1.19 [1.09 to 1.30]) had the most significant association with OS (P = .0003). Addition of baseline GEN and inflammatory plasma cytokine biomarkers in predicting LF, respectively, increased AUC by 0.06 (from 0.73 to 0.79) and 0.07 (from 0.77 to 0.84). In predicting OS, inclusion of midtreatment complete blood count biomarkers increased AUC from 0.72 to 0.80, along with significant boosts in likelihood ratio and predictive variance. CONCLUSION: Inclusion of serial blood biomarkers leads to significant gain in predicting response to liver metastasis stereotactic body radiation therapy and can guide treatment personalization.

Targeting the DNA replication stress phenotype of KRAS mutant cancer cells.

Mutant KRAS is a common tumor driver and frequently confers resistance to anti-cancer treatments such as radiation. DNA replication stress in these tumors may constitute a therapeutic liability but is poorly understood. Here, using single-molecule DNA fiber analysis, we first characterized baseline replication stress in a panel of unperturbed isogenic and non-isogenic cancer cell lines. Correlating with the observed enhanced replication stress we found increased levels of cytosolic double-stranded DNA in KRAS mutant compared to wild-type cells. Yet, despite this phenotype replication stress-inducing agents failed to selectively impact KRAS mutant cells, which were protected by CHK1. Similarly, most exogenous stressors studied did not differentially augment cytosolic DNA accumulation in KRAS mutant compared to wild-type cells. However, we found that proton radiation was able to slow fork progression and preferentially induce fork stalling in KRAS mutant cells. Proton treatment also partly reversed the radioresistance associated with mutant KRAS. The cellular effects of protons in the presence of KRAS mutation clearly contrasted that of other drugs affecting replication, highlighting the unique nature of the underlying DNA damage caused by protons. Taken together, our findings provide insight into the replication stress response associated with mutated KRAS, which may ultimately yield novel therapeutic opportunities.

Prompt gamma imaging for the identification of regional proton range deviations due to anatomic change in a heterogeneous region.

OBJECTIVES: Prompt gamma (PG) imaging has previously been demonstrated for use in proton range verification of a brain treatment with a homogeneous target region. In this study, the feasibility of PG imaging to detect anatomic change within a heterogeneous region is presented. METHODS: A prompt gamma camera recorded several fractions of a patient treatment to the base of skull. An evaluation CT revealed a decrease in sinus cavity filling during the treatment course. Comparison of PG profiles between measurement and simulation was performed to investigate range variations between planned and measured pencil beam spot positions. RESULTS: For one field, an average over range of 3 mm due to the anatomic change could be detected for a subset of spots traversing the sinus cavity region. The two other fields appeared less impacted by the change but predicted range variations could not be detected. These results were partially consistent with the simulations of the evaluation CT. CONCLUSION: We report the first clinical application of PG imaging that detected some of the expected small regional proton range deviations due to anatomic change in a heterogeneous region. However, several limitations exist with the technology that may limit its sensitivity to detect range deviations in heterogeneous regions. ADVANCES IN KNOWLEDGE: We report on the first detection of range variations due to anatomic change in a heterogeneous region using PGI. The results confirm the feasibility of using PG-based range verification in highly heterogeneous target regions to identify deviations from the treatment plan.

Computer animation body surface analysis of total skin electron radiation therapy dose homogeneity via Cherenkov imaging.

Purpose: Quality assurance (QA) of dose homogeneity in total skin electron therapy (TSET) is challenging since each patient is positioned in six standing poses with two beam angles. Our study tested the feasibility of a unique approach for TSET QA through computational display of the cumulative dose, constructed and synthesized by computer animation methods. Approach: Dose distributions from Cherenkov emission images were projected onto a scanned 3D body model. Topographically mapped surfaces of the patient were recorded in each of six different delivery positions, while a Cherenkov camera acquired images. Computer animation methods allowed a fitted 3D human body model of the patient to be created with deformation of the limbs and torso to each position. A two-dimensional skin map was extracted from the 3D model of the full surface of the patient. This allowed the dose mapping to be additively accumulated independent of body position, with the total dose summed in a 2D map and reinterpreted on the 3D body display. Results: For the body model, the mean Hausdorff error distance was below 2 cm, setting the spatial accuracy limit. The dose distribution over the patient's 3D model generally matched the Cherenkov/dose images. The dose distribution mapping was estimated to be near 1.5 cm accuracy based upon a phantom study. The body model must most closely match at the edges of the mesh to ensure that high dose gradients are not projected onto the wrong location. Otherwise 2 to 3 cm level errors in positioning in the mesh do not appear to cause larger than 5% dose errors. The cumulative dose images showed regions of overlap laterally and regions of low intensity in the posterior arms. Conclusions: The proposed modeling and animation can be used to visualize and analyze the accumulated dose in TSET via display of the summed dose/Cherenkov images on a single body surface.

Input and output of cadmium (Cd) for paddy soil in central south China: fluxes, mass balance, and model predictions.

It is important to provide a more comprehensive understanding of cadmium (Cd) input and output in different contamination zones. In this study, we choose 15 sampling areas in three types of contamination zones (industrial and mining, suburb, and rural) to systematically study the inventory of soil Cd input and output in Changzhutan (CZT) urban agglomerations, Hunan Province, China. The results showed that the value of total Cd input in industrial and mining (34.58 g/ha/year) was respectively about 2 and 3 times of that in suburb and in rural. Meanwhile, the total output flux in industrial and mining also presented highest value (38.67 g/ha/year) among the zones. As for the contributions, atmospheric deposition was responsible for 85-89% of the total input fluxes, which was significantly higher than those of irrigation water and fertilizer. Crop harvesting, especially straw removal, was the dominant output pathway, contributing 66-78%. Moreover, Cd annual balance illustrated that the net input fluxes under straw removal scenario were negative in all zones, and it was opposite under straw returning scenario. Further, the changes of soil Cd concentrations under straw returning and straw removal scenario were compared by a dynamic mathematical model. The modeling results presented that the soil Cd content continued to increase under straw returning in 100 years, while it was declining under straw removal scenario. This prediction indicated straw removal was an important remediation for Cd-polluted paddy soil, especially in Hunan. Nevertheless, more treatment measures need to conduct to reach the safety limits in paddy soil.