Hesperetin derivative 2a inhibits lipopolysaccharide-induced acute liver injury in mice via downregulation of circDcbld2.

Acute liver injury (ALI) is a complex, life-threatening inflammatory liver disease, and persistent liver damage leads to rapid decline and even failure of liver function. However, the pathogenesis of ALI is still not fully understood, and no effective treatment has been discovered. Recent evidence shows that many circular RNAs (circRNAs) are associated with the occurrence of liver diseases. In this study we investigated the mechanisms of occurrence and development of ALI in lipopolysaccharide (LPS)-induced ALI mice. We found that expression of the circular RNA circDcbld2 was significantly elevated in the liver tissues of ALI mice and LPS-treated RAW264.7 cells. Knockdown of circDcbld2 markedly alleviates LPS-induced inflammatory responses in ALI mice and RAW264.7 cells. We designed and synthesized a series of hesperidin derivatives for circDcbld2, and found that hesperetin derivative 2a (HD-2a) at the concentrations of 2, 4, 8 µM effectively inhibited circDcbld2 expression in RAW264.7 cells. Administration of HD-2a (50, 100, 200 mg/kg. i.g., once 24 h in advance) effectively relieved LPS-induced liver dysfunction and inflammatory responses. RNA sequencing analysis revealed that the anti-inflammatory and hepatoprotective effects of HD-2a were mediated through downregulating circDcbld2 and suppressing the JAK2/STAT3 pathway. We conclude that HD-2a downregulates circDcbld2 to inhibit the JAK2/STAT3 pathway, thereby inhibiting the inflammatory responses in ALI. The results suggest that circDcbld2 may be a potential target for the prevention and treatment of ALI, and HD-2a may have potential as a drug for the treatment of ALI.

Polyhydroxylated Spirostanol Saponins from the Rhizomes of Paris dulongensis.

Three new polyhydroxylated spirostanol steroidal saponins, dulongenosides B-D (2-4), along with 14 known compounds, dulongenoside A (1), padelaoside B (5), parisyunnanoside G (6), polyphyllin D (7), ophiopogonin C' (8), formosanin C (9), dioscin (10), paris saponin VII (11), paris H (12), parisyunnanoside I (13), protodioscin (14), proprotogracillin (15), crustecdysone (16), and stigmasterol-3-O-ß-d-glucopyranoside (17), were isolated from the rhizomes of Paris dulongensis (Melanthiaceae). Their chemical structures were elucidated based on extensive analyses of NMR and MS data and acidic hydrolyses. The isolates were evaluated for their cytotoxicity to five human cancer cell lines (HL-60, SW480, MDA-MB-231, A549, and A549/Taxol) and the normal human bronchial epithelial cell line BEAS-2B by the MTS test. Compounds 7-12 and 14 showed cytotoxic activity, with IC50 values ranging from 0.20 to 4.35 µM. Proprotogracillin selectively inhibited A549 (IC50=0.58 µM) and A549/Taxol (IC50=0.74 µM) cells, with no significant cytotoxic activity against HL-60, SW480, MDA-MB-231, or BEAS-2B cells, with IC50 values greater than 40 µM.

Radiomics-enhanced early regression index for predicting treatment response in rectal cancer: a multi-institutional 0.35 T MRI-guided radiotherapy study.

PURPOSE: The accurate prediction of treatment response in locally advanced rectal cancer (LARC) patients undergoing MRI-guided radiotherapy (MRIgRT) is essential for optimising treatment strategies. This multi-institutional study aimed to investigate the potential of radiomics in enhancing the predictive power of a known radiobiological parameter (Early Regression Index, ERITCP) to evaluate treatment response in LARC patients treated with MRIgRT. METHODS: Patients from three international sites were included and divided into training and validation sets. 0.35 T T2*/T1-weighted MR images were acquired during simulation and at each treatment fraction. The biologically effective dose (BED) conversion was used to account for different radiotherapy schemes: gross tumour volume was delineated on the MR images corresponding to specific BED levels and radiomic features were then extracted. Multiple logistic regression models were calculated, combining ERITCP with other radiomic features. The predictive performance of the different models was evaluated on both training and validation sets by calculating the receiver operating characteristic (ROC) curves. RESULTS: A total of 91 patients was enrolled: 58 were used as training, 33 as validation. Overall, pCR was observed in 25 cases. The model showing the highest performance was obtained combining ERITCP at BED = 26 Gy with a radiomic feature (10th percentile of grey level histogram, 10GLH) calculated at BED = 40 Gy. The area under ROC curve (AUC) of this combined model was 0.98 for training set and 0.92 for validation set, significantly higher (p = 0.04) than the AUC value obtained using ERITCP alone (0.94 in training and 0.89 in validation set). CONCLUSION: The integration of the radiomic analysis with ERITCP improves the pCR prediction in LARC patients, offering more precise predictive models to further personalise 0.35 T MRIgRT treatments of LARC patients.

Calcium signal regulated carbohydrate metabolism in wheat seedlings under salinity stress.

This study aimed to explore the mechanism by which calcium (Ca) signal regulated carbohydrate metabolism and exogenous Ca alleviated salinity toxicity. Wheat seedlings were treated with sodium chloride (NaCl, 150 mM) alone or combined with 500 µM calcium chloride (CaCl2), lanthanum chloride (LaCl3) and/or ethylene glycol tetraacetic acid (EGTA) to primarily analyse carbohydrate starch and sucrose metabolism, as well as Ca signaling components. Treatment with NaCl, EGTA, or LaCl3 alone retarded wheat-seedling growth and decreased starch content accompanied by weakened ribulose-1,5-bisphosphate carboxylation/oxygenase (Rubisco) and Rubisco activase activities, as well as enhanced glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, alpha-amylase, and beta-amylase activities. However, it increased the sucrose level, up-regulated the sucrose phosphate synthase (SPS) and sucrose synthase (SuSy) activities and TaSPS and TaSuSy expression together, but down-regulated the acid invertase (SA-Inv) and alkaline/neutral invertase (A/N-Inv) activities and TaSA-Inv and TaA/N-Inv expression. Except for unchanged A/N-Inv activities and TaA/N-Inv expression, adding CaCl2 effectively blocked the sodium salt-induced changes of these parameters, which was partially eliminated by EGTA or LaCl3 presence. Furthermore, NaCl treatment also significantly inhibited Ca-dependent protein kinases and Ca2+-ATPase activities and their gene expression in wheat leaves, which was effectively relieved by adding CaCl2. Taken together, CaCl2 application effectively alleviated the sodium salt-induced retardation of wheat-seedling growth by enhancing starch anabolism and sucrose catabolism, and intracellular Ca signal regulated the enzyme activities and gene expression of starch and sucrose metabolism in the leaves of sodium salt-stressed wheat seedlings.

Enhancingß-Ga2O3-film ultraviolet detectors via RF magnetron sputtering with seed layer insertion onc-plane sapphire substrate.

Gallium oxide (Ga2O3) possesses a band gap of approximately 4.9 eV, aligning its detection wavelength within the solar-blind region, making it an ideal semiconductor material for solar-blind photodetectors. This study aims to enhance the performance of Ga2O3ultraviolet (UV) detectors by pre-depositing a Ga2O3seed layer on ac-plane sapphire substrate. The x-ray diffraction and x-ray photoelectron spectroscopy analyses validated that the deposited films, following high-temperature annealing, comprisedß-Ga2O3. Comparing samples with and without a 20 nm seed layer, it was found that the former exhibited fewer oxygen defects and substantially improved crystal quality. The incorporation of the seed layer led to the realization of detectors with remarkably low dark current (≤15.3 fA). Moreover, the photo-to-dark current ratio was enhanced by 30% (surpassing 1.3 × 104) and the response/recovery time reduced to 0.9 s/0.01 s, indicating faster performance. Furthermore, these detectors demonstrated higher responsivity (4.8 mA W-1), improved detectivity (2.49 × 1016Jones), and excellent solar-blind characteristics. This study serves as a foundational stepping toward achieving high-qualityß-Ga2O3thin film and UV detector arrays.

PPAR-γ alleviates the inflammatory response in TNF-α-induced fibroblast-like synoviocytes by binding to p53 in rheumatoid arthritis.

Rheumatoid arthritis (RA) is characterized by synovial inflammation, synoviocyte expansion and damage to cartilage and bone. We recently reported that peroxisome proliferator-activated receptor (PPAR)-γ inhibited the proliferation and activation of fibroblast-like synoviocytes (FLS), and was downregulated in RA synovial. In this study we investigated the role of PPAR-γ in RA and the underlying mechanisms. Adjuvant-induced arthritis (AIA) was induced in rats; from D15, AIA rats were orally administered pioglitazone (30 mg·kg-1·d-1) or rosiglitazone (4 mg·kg-1·d-1) for 14 days. Collagen-induced arthritis (CIA) was induced in wild-type and Ppar-γ+/- mice. We showed that the expression of PPAR-γ was significantly reduced, whereas that of TNF-α was markedly increased in human RA FLS. In CIA mice, knockdown of PPAR-γ expression (Ppar-γ+/-) aggravated the ankle inflammation. Similarly, T0070907 (a PPAR-γ antagonist) or si-PPAR-γ promoted the activation and inflammation of TNF-α-induced FLS in vitro. On the contrary, administration of PPAR-γ agonist pioglitazone or rosiglitazone, or injection of ad-Ppar-γ into the ankle of AIA rat in vivo induced overexpression of PPAR-γ, reduced the paw swelling and inflammation, and downregulated activation and inflammation of FLS in RA. Interesting, injection of ad-Ppar-γ into the ankle also reversed the ankle inflammation in Ppar-γ+/- CIA mice. We conducted RNA-sequencing and KEGG pathway analysis, and revealed that PPAR-γ overexpression was closely related to p53 signaling pathway in TNF-α-induced FLS. Co-IP study confirmed that p53 protein was bound to PPAR-γ in RA FLS. Taken together, PPAR-γ alleviates the inflammatory response of TNF-α-induced FLS by binding p53 in RA.

Copper stress-induced phytotoxicity associated with photosynthetic characteristics and lignin metabolism in wheat seedlings.

Copper (Cu) pollution is one of environmental problems that adversely affects the growth and development of plants. However, knowledge of lignin metabolism associated with Cu-induced phytotoxicity mechanism is insufficient. The objective of this study was to reveal the mechanisms underlying Cu-induced phytotoxicity by evaluating changes in the photosynthetic characteristics and lignin metabolism in the seedlings of wheat cultivar 'Longchun 30'. Treatment with varying concentrations of Cu clearly retarded seedling growth, as demonstrated by a reduction in the growth parameters. Cu exposure reduced the photosynthetic pigment content, gas exchange parameters, and chlorophyll fluorescence parameters, including the maximum photosynthetic efficiency, potential efficiency of photosystem II (PS II), photochemical efficiency of PS II in light, photochemical quenching, actual photochemical efficiency, quantum yield of PS II electron transport, and electron transport rate, but notably increased the nonphotochemical quenching and quantum yield of regulatory energy dissipation. Additionally, a significant increase was observed in the amount of cell wall lignin in wheat leaves and roots under Cu exposure. This increase was positively associated with the up-regulation of enzymes related to lignin synthesis, such as phenylalanine ammonia-lyase, 4-coumarate:CoA ligase, cinnamyl alcohol dehydrogenase, laccase, cell wall bound (CW-bound) guaiacol peroxidase, and CW-bound conifer alcohol peroxidase, and TaPAL, Ta4CL, TaCAD, and TaLAC expression. Correlation analysis revealed that lignin levels in the cell wall were negatively correlated with the growth of wheat leaves and roots. Taken together, Cu exposure inhibited photosynthesis in wheat seedlings, resulting from a reduction in photosynthetic pigment content, light energy conversion, and photosynthetic electron transport in the leaves of Cu-stressed seedlings, and the Cu-inhibitory effect on seedling growth was related to the inhibition of photosynthesis and an increase in cell wall lignification.

Assessment of sulfamethoxazole toxicity to marine mussels (Mytilus galloprovincialis): Combine p38-MAPK signaling pathway modulation with histopathological alterations.

Sulfamethoxazole (SMX), is a ubiquitous antibiotic in the aquatic environment and received concerns on its health hazards, especially its sub-lethal effects on non-target organisms which were remained largely unknown. In the present study, in order to investigate SMX induced tissue damages and reveal underlying mechanisms, marine mussels, Mytilus galloprovincialis were challenged to SMX series (0.5, 50 and 500 µg/L) for six-days followed by six-day-recovery. Comprehensive histopathological alteration (including qualitative, semi-quantitative and quantitative indices), together with transcriptional and (post-) translational responses of key factors (p38, NFκB and p53) in the p38-MAPK signaling pathway were analyzed in gills and digestive glands. Tissue-specific responses were clearly investigated with gills showing more prompt responses and digestive glands showing higher tolerance to SMX. The histopathology showed that SMX triggered inflammatory damages in both tissues and quantitative analysis revealed more significant responses, suggesting its potential as a valuable health indicator. SMX activated expressions of p38, NFκB and p53 at transcriptional and (post-) translational levels, especially after exposed to low level SMX, evidenced by p38 coupled with NFκB/p53 regulation on immunity defense in mussels. Less induction of targeted molecules under severe SMX exposure indicated such signaling transduction may not be efficient enough and can result in inflammatory damages. Taken together, this study expanded the understanding of aquatic SMX induced health risk in marine mussels and the underlying regulation mechanism through p38 signaling transduction.

Dosimetric evaluation of respiratory gating on a 0.35-T magnetic resonance-guided radiotherapy linac.

PURPOSE: The commercial 0.35-T magnetic resonance imaging (MRI)-guided radiotherapy vendor ViewRay recently introduced upgraded real-time imaging frame rates based on compressed sensing techniques. Furthermore, additional motion tracking algorithms were made available. Compressed sensing allows for increased image frame rates but may compromise image quality. To assess the impact of this upgrade on respiratory gating accuracy, we evaluated gated dose distributions pre- and post-upgrade using a motion phantom and radiochromic film. METHODS: Seven motion waveforms (four artificial, two patient-derived free-breathing, and one breath-holding) were used to drive an MRI-compatible motion phantom. A treatment plan was developed to deliver a 3-cm diameter spherical dose distribution typical of a stereotactic body radiotherapy plan. Gating was performed using 4-frames per second (fps) imaging pre-upgrade on the "default" tracking algorithm and 8-fps post-upgrade using the "small mobile targets" (SMT) and "large deforming targets" (LDT) tracking algorithms. Radiochromic film was placed in a moving insert within the phantom to measure dose. The planned and delivered dose distributions were compared using the gamma index with 3%/3-mm criteria. Dose-area histograms were produced to calculate the dose to 95% (D95) of the sphere planning target volume (PTV) and two simulated gross tumor volumes formed by contracting the PTV by 3 and 5 mm, respectively. RESULTS: Gamma pass rates ranged from 18% to 93% over the 21 combinations of breathing trace and gating conditions examined. D95 ranged from 206 to 514 cGy. On average, the LDT algorithm yielded lower gamma and D95 values than the default and SMT algorithms. CONCLUSION: Respiratory gating at 8 fps with the new tracking algorithms provides similar gating performance to the original algorithm with 4 fps, although the LDT algorithm had lower accuracy for our non-deformable target. This indicates that the choice of deformable image registration algorithm should be chosen deliberately based on whether the target is rigid or deforming.

Magnetic resonance imaging-guided stereotactic body radiotherapy for prostate cancer (mirage): a phase iii randomized trial.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is becoming increasingly used in treating localized prostate cancer (PCa), with evidence showing similar toxicity and efficacy profiles when compared with longer courses of definitive radiation. Magnetic resonance imaging (MRI)-guided radiotherapy has multiple potential advantages over standard computed tomography (CT)-guided radiotherapy, including enhanced prostate visualization (abrogating the need for fiducials and MRI fusion), enhanced identification of the urethra, the ability to track the prostate in real-time, and the capacity to perform online adaptive planning. However, it is unknown whether these potential advantages translate into improved outcomes. This phase III randomized superiority trial is designed to prospectively evaluate whether toxicity is lower after MRI-guided versus CT-guided SBRT. METHODS: Three hundred men with localized PCa will be randomized in a 1:1 ratio to SBRT using CT or MRI guidance. Randomization will be stratified by baseline International Prostate Symptom Score (IPSS) (≤15 or > 15) and prostate gland volume (≤50 cc or > 50 cc). Five fractions of 8 Gy will be delivered to the prostate over the course of fourteen days, with or without hormonal therapy and elective nodal radiotherapy (to a dose of 5 Gy per fraction) as per the investigator's discretion. The primary endpoint is the incidence of physician-reported acute grade ≥ 2 genitourinary (GU) toxicity (during the first 90 days after SBRT), as assessed by the CTCAE version 4.03 scale. Secondary clinical endpoints include incidence of acute grade ≥ 2 gastrointestinal (GI) toxicity, 5-year cumulative incidences of physician-reported late grade ≥ 2 GU and GI toxicity, temporal changes in patient-reported quality of life (QOL) outcomes, 5-year biochemical recurrence-free survival and the proportion of fractions of MRI-guided SBRT in which online adaptive radiotherapy is used. DISCUSSION: The MIRAGE trial is the first randomized trial comparing MRI-guided with standard CT-guided SBRT for localized PCa. The primary hypothesis is that MRI-guided SBRT will lead to an improvement in the cumulative incidence of acute grade ≥ 2 GU toxicity when compared to CT-guided SBRT. The pragmatic superiority design focused on an acute toxicity endpoint will allow an early comparison of the two technologies. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04384770. Date of registration: May 12, 2020. https://clinicaltrials.gov/ct2/show/NCT04384770 PROTOCOL VERSION: Version 2.1, Aug 28, 2020.

Clinical assessment of geometric distortion for a 0.35T MR-guided radiotherapy system.

PURPOSE: To estimate the overall spatial distortion on clinical patient images for a 0.35 T MR-guided radiotherapy system. METHODS: Ten patients with head-and-neck cancer underwent CT and MR simulations with identical immobilization. The MR images underwent the standard systematic distortion correction post-processing. The images were rigidly registered and landmark-based analysis was performed by an anatomical expert. Distortion was quantified using Euclidean distance between each landmark pair and tagged by tissue interface: bone-tissue, soft tissue, or air-tissue. For baseline comparisons, an anthropomorphic phantom was imaged and analyzed. RESULTS: The average spatial discrepancy between CT and MR landmarks was 1.15 ± 1.14 mm for the phantom and 1.46 ± 1.78 mm for patients. The error histogram peaked at 0-1 mm. 66% of the discrepancies were <2 mm and 51% <1 mm. In the patient data, statistically significant differences (p-values < 0.0001) were found between the different tissue interfaces with averages of 0.88 ± 1.24 mm, 2.01 ± 2.20 mm, and 1.41 ± 1.56 mm for the air/tissue, bone/tissue, and soft tissue, respectively. The distortion generally correlated with the in-plane radial distance from the image center along the longitudinal axis of the MR. CONCLUSION: Spatial distortion remains in the MR images after systematic distortion corrections. Although the average errors were relatively small, large distortions observed at bone/tissue interfaces emphasize the need for quantitative methods for assessing and correcting patient-specific spatial distortions.

Multishot diffusion-prepared magnitude-stabilized balanced steady-state free precession sequence for distortion-free diffusion imaging.

PURPOSE: To develop and evaluate a multishot diffusion-prepared (DP) magnitude-stabilized balanced steady-state free precession (bSSFP) diffusion imaging sequence with improved geometric fidelity. METHODS: A signal spoiler (magnitude stabilizer; MS) was implemented in a DP-bSSFP diffusion sequence. Effects of magnitude stabilizers with respect to phase errors were simulated using Bloch simulation. Phantom study was conducted to compare the apparent diffusion coefficient (ADC) accuracy and geometric reliability, quantified using target registration error (TRE), with diffusion-weighted single-shot echo-planar imaging (DW-ssEPI). Six volunteers were recruited. DW-ssEPI, DP-bSSFP with and without ECG triggering, and DP-MS-bSSFP with and without ECG triggering were acquired 10 times with b = 500 s/mm2 in a single-shot manner to evaluate magnitude variability. Diffusion trace images and diffusion tensor images were acquired using a 4-shot DP-MS-bSSFP. RESULTS: Simulation showed that the DP-MS-bSSFP approach is insensitive to phase errors. The DP-MS-bSSFP approach had satisfactory ADC accuracy on the phantom with <5% difference with DW-ssEPI. The mean/max TRE for DW-ssEPI was 2.31/4.29 mm and was 0.51/1.20 mm for DP-MS-bSSFP. In the repeated single-shot study, DP-bSSFP without ECG triggering had severe signal void artifacts and exhibited a nonrepeatable pattern, which can be partially mitigated by ECG triggering. Adding the MS provided stable signal magnitude across all repetitions. High-quality ADC maps and color-coded fractional anisotropy maps were generated using the 4-shot DP-MS-bSSFP. The mean/max TRE was 2.89/10.80 mm for DW-ssEPI and 0.59/1.69 mm for DP-MS-bSSFP. Good agreements of white matter ADC, cerebrospinal fluid ADC, and white matter fractional anisotropy value were observed between DP-MS-bSSFP and DW-ssEPI. CONCLUSION: The proposed DP-MS-bSSFP approach provided high-quality diffusion-weighted and diffusion-tensor images with minimal geometric distortion.

Development and evaluation of a C-ELISA for rapid detection of antibody to AIV- H7.

Since 2013, the H7 subtype avian influenza virus (AIV-H7) has seriously endangered human life and health, and has had a serious impact on the poultry industry in China. A competitive enzyme-linked immunosorbent assay (C-ELISA) which detects the antibody for AIV-H7 was developed, basing on a monoclonal antibody (mAb) against the neutralizing epitopes on hemagglutinin (HA)gene. Twelve hybridoma cell lines were screened by cell fusion. Hemagglutination inhibition (HI) assay and indirect ELISA were used to identify the competitive effect of the mAbs. High-affinity mAb 1H11 was selected as a competitive antibody. The reaction conditions for the C-ELISA were optimized for AIV-H7 antibody detection. The cross-reactivity of the C-ELISA was determined by AIV-(H1H15), NDV, IBV and IBDV positive serum. A total of 1294 field samples (chicken (462), duck (318), goose (219), quail (203) and pigeon (92) were simultaneously detected by C-ELISA and HI assay. The C-ELISA was found to have a high specificity of 93.23% and a sensitivity of 96.24%. These results reveal a positive coincidence between C-ELISA and HI assay at a coincidence rate of 97.52%. In addition, It confirmed that this method can be used for the diagnosis of AIV-H7 antibodies from chicken, ducks, goose, quail and pigeons.

Effects of Corrective Feedback on EFL Learners' Acquisition of Third-Person Singular Form and the Mediating Role of Cognitive Style.

The present study investigated the effectiveness of recasts and prompts on the acquisition of the English third-person singular form and the mediating role of cognitive style on the effects of feedback. One hundred and seventy-five college students from four intact classes were assigned to four groups: form-focused instruction with recast (FFI-recast), FFI with prompt (FFI-prompt), FFI, and control. The group embedded figures test (Witkin et al. in Rev Educ Res 47:1-64, 1977) was adopted to test learners' cognitive style (field dependence/independence). The results show that the FFI-prompt group outperformed the FFI-recast group and the control group on the immediate post-test; the FFI-prompt group also achieved significantly higher scores than the other groups on the delayed post-test in the written test. However, no significant difference was found among groups in the text-completion test. Regression analyses reveal that in the text-completion test, field dependence/independence mediates the effect of recasts on the immediate post-test.

Cadmium stress tolerance in wheat seedlings induced by ascorbic acid was mediated by NO signaling pathways.

Ascorbic acid (AsA) and nitric oxide (NO) are well known and widespread antioxidants and gaseous molecules that regulate plant tolerance to several stresses. However, the relationship between them in plant response to stress, especially heavy stress, is largely unclear. This study demonstrated that both AsA and NO could enhance the tolerance of wheat seedlings to cadmium stress evidenced by root length change, which resulted from their roles in maintaining the balance in reactive oxygen species (ROS) and reducing the absorption of Cd. Furthermore, exogenous AsA led to a significant increase of NO content and endogenous AsA content in wheat roots, which could be weakened by the NO scavenger c-PTIO. In addition, c-PTIO also inhibits the NO-induced production of endogenous AsA. Although the AsA synthesis inhibitor lycorine significantly inhibited the inductive effect of exogenous AsA on endogenous AsA production, it has little effect on NO content. In addition, we found that the protective effects of NO and AsA on Cd stress were removed by c-PTIO and lycorine. These results indicated that NO accumulation could be necessary for exogenous AsA-induced cadmium tolerance and endogenous AsA production, and the exogenous AsA-induced endogenous AsA production was likely mediated by NO signaling pathways and together they induced the tolerance of wheat to cadmium stress.

Dosimetric validation of a magnetic resonance image gated radiotherapy system using a motion phantom and radiochromic film.

PURPOSE: Magnetic resonance image (MRI) guided radiotherapy enables gating directly on the target position. We present an evaluation of an MRI-guided radiotherapy system's gating performance using an MRI-compatible respiratory motion phantom and radiochromic film. Our evaluation is geared toward validation of our institution's clinical gating protocol which involves planning to a target volume formed by expanding 5 mm about the gross tumor volume (GTV) and gating based on a 3 mm window about the GTV. METHODS: The motion phantom consisted of a target rod containing high-contrast target inserts which moved in the superior-inferior direction inside a body structure containing background contrast material. The target rod was equipped with a radiochromic film insert. Treatment plans were generated for a 3 cm diameter spherical planning target volume, and delivered to the phantom at rest and in motion with and without gating. Both sinusoidal trajectories and tumor trajectories measured during MRI-guided treatments were used. Similarity of the gated dose distribution to the planned, motion-frozen, distribution was quantified using the gamma technique. RESULTS: Without gating, gamma pass rates using 4%/3 mm criteria were 22-59% depending on motion trajectory. Using our clinical standard of repeated breath holds and a gating window of 3 mm with 10% target allowed outside the gating boundary, the gamma pass rate was 97.8% with 3%/3 mm gamma criteria. Using a 3 mm window and 10% allowed excursion, all of the patient tumor motion trajectories at actual speed resulting in at least 95% gamma pass rate at 4%/3 mm. CONCLUSIONS: Our results suggest that the device can be used to compensate respiratory motion using a 3 mm gating margin and 10% allowed excursion results in conjunction with repeated breath holds. Full clinical validation requires a comprehensive evaluation of tracking performance in actual patient images, outside the scope of this study.

Interaction of nitric oxide and reactive oxygen species and associated regulation of root growth in wheat seedlings under zinc stress.

The inhibition of root growth was investigated in wheat seedlings exposed to 3mM zinc (Zn). Zn treatment with or without 250 µM 2-phenyl-4,4,5,5,-tetrame-thylimidazoline-3-oxide-1-oxyl (PTIO) or 10 µM diphenylene iodonium (DPI) significantly inhibited growth, increased malondialdehyde content and lowered cell viability in roots. The most prominent changes of these three parameters at Zn+DPI treatment could be partly blocked by high PTIO concentration (1mM). The production of nitric oxide (NO) and hydrogen peroxide (H2O2) influenced each other under different treatments, with the highest NO level and the highest H2O2 accumulation in Zn+DPI-treated roots. Compared with Zn-stressed roots, catalase, soluble peroxidase (POD), ascorbate peroxidase and superoxide dismutase decreased in Zn+DPI-treated roots, suggesting that ROS generation from plasma membrane (PM) NADPH oxidase was associated with the regulation of antioxidant enzyme activities. Additionally, Zn-treated roots exhibited significant decreases in cell wall-bound POD, diamine oxidase and polyamine oxidase activities. Our results suggested that Zn-induced effects on root growth resulted from NO interaction with H2O2 and that Zn+DPI-induced strongest inhibition could be explained by the highest increase in the endogenous NO content and the reduction of extracellular ROS production.

Comparative study of integrated bio-responses in deep-sea and nearshore mussels upon abiotic condition changes: Insight into distinct regulation and adaptation.

Deep-sea mussels, one of the dominant species in most deep-sea ecosystems, have long been used as model organisms to investigate the adaptations and symbiotic relationships of deep-sea macrofauna under laboratory conditions due to their ability to survive under atmospheric pressure. However, the impact of additional abiotic conditions beyond pressure, such as temperature and light, on their physiological characteristics remains unknown. In this study, deep-sea mussels (Gigantidas platifrons) from cold seep of the South China Sea, along with nearshore mussels (Mytilus coruscus) from the East China Sea, were reared in unfavorable abiotic conditions for up to 8 days. Integrated biochemical indexes including antioxidant defense, immune ability and energy metabolism were investigated in the gill and digestive gland, while cytotoxicity was determined in hemocytes of both types of mussels. The results revealed mild bio-responses in two types of mussels in the laboratory, represented by the effective antioxidant defense with constant total antioxidant capability level and malondialdehyde content. There were also disparate adaptations in deep-sea and nearshore mussels. In deep-sea mussels, significantly increased immune response and energy reservation were observed in gills, together with the elevated cytotoxicity in hemocytes, implying the more severe biological adaptation was required, mainly due to the symbiotic bacteria loss under laboratory conditions. On the contrary, insignificant biological responses were exhibited in nearshore mussels except for the increased energy consumption, indicating the trade-off strategy to use more energy to deal with potential stress. Overall, this comparative study highlights the basal bio-responses of deep-sea and nearshore mussels out of their native environments, providing evidence that short-term culture of both mussels under easily achievable laboratory conditions would not dramatically alter their biological status. This finding will assist in broadening the application of deep-sea mussels as model organism in future research regardless of the specialized research equipment.

Quantitative MRI on MR-Linacs: Towards Biological Image-Guided Adaptive Radiotherapy.

Recognizing the potential of quantitative imaging biomarkers (QIBs) in radiotherapy, many studies have investigated the prognostic value of quantitative MRI (qMRI). With the introduction of MRI-guided radiotherapy systems, the practical challenges of repeated imaging have been substantially reduced. Since patients are treated inside an MRI scanner, acquisition of qMRI can be done during each fraction with limited or no prolongation of the fraction duration. In this review paper, we identify the steps that need been taken to move from MR as an imaging technique to a useful biomarker for MRI-guided radiotherapy (MRgRT).

Dosimetric predictors for genitourinary toxicity in MR-guided stereotactic body radiation therapy (SBRT): Substructure with fraction-wise analysis.

BACKGROUND: MR-guided radiation therapy (MRgRT) systems provide superior soft tissue contrast than x-ray based systems and can acquire real-time cine for treatment gating. These features allow treatment planning margins to be reduced, allowing for improved critical structure sparing and reduced treatment toxicity. Despite this improvement, genitourinary (GU) toxicity continues to affect many patients. PURPOSE: (1) To identify dosimetric predictors, potentially in combination with clinical parameters, of GU toxicity following SBRT by leveraging MRgRT to accurately monitor daily dose, beyond predicted dose calculated during planning. (2) Improve awareness of toxicity-sensitive bladder substructures, specifically the trigone and urethra. METHODS: Sixty-nine prostate cancer patients (NCT04384770 clinical trial) were treated on a ViewRay MRIdian MRgRT system, with 40 Gy prescribed to 95% of the PTV in over five fractions. Overall, 17 (24.6%) prostate patients reported acute grade 2 GU toxicity. The CTV, PTV, bladder, bladder wall, trigone, urethra, rectum, and rectal wall were contoured on the planning and daily treatment MRIs. Planning and daily treatment DVHs (0.1 Gy increments), organ doses (min, max, mean), and organ volumes were recorded. Daily dose was estimated by transferring the planning dose distributions to the daily MRI based on the daily setup alignment. Patients were partitioned into a training (55) and testing set (14). Dose features were pre-filtered using a t-test followed by maximum relevance minimum redundancy (MRMR) algorithm. Logistic regression was investigated with regularization to select dosimetric predictors. Specifically, two approaches: time-group least absolute shrinkage and selection (LASSO), and interactive grouped greedy algorithm (IGA) were investigated. Shared features across the planning and five treatment fractions were grouped to encourage consistency and stability. The conventional flat non-temporally grouped LASSO was also evaluated to provide a solid benchmark. After feature selection, a final logistic regression model was trained. Dosimetric regression models were compared to a clinical regression model with only clinical parameters (age, baseline IPSS, prostate gland size, ADT usage, etc.) and a hybrid model, combining the best performing dosimetric features with the clinical parameters, was evaluated. Final model performance was evaluated on the testing set using accuracy, sensitivity, and specificity determined by the optimal threshold of the training set. RESULTS: IGA had the best testing performance with an accuracy/sensitivity/specificity of 0.79/0.67/0.82, selecting 12 groups covering the bladder (V19.8 Gy, V20.5 Gy), bladder wall (19.7 Gy), trigone (15.9, 18.2, 43.3 Gy), urethra (V41.4 Gy, V41.7 Gy), CTV (V41.9 Gy), rectum (V8.5 Gy), and rectal wall (1.2, 44.1 Gy) dose features. Absolute bladder V19.8 Gy and V20.5 Gy were the most important features, followed by relative trigone 15.9  and 18.2 Gy. Inclusion of clinical parameters in the hybrid model with IGA did not significantly change regression performance. CONCLUSION: Overall, IGA feature selection resulted in the best GU toxicity prediction performance. This exploratory study demonstrated the feasibility of identification and analysis of dosimetric toxicity predictors with awareness to sensitive substructures and daily dose to potentially provide consistent and stable dosimetric metrics to guide treatment planning. Further patient accruement is warranted to further assess dosimetric predictor and perform validation.