Quantitative assessment of intertarget position variations based on 4D-CT and 4D-CBCT simulations in single-isocenter multitarget lung stereotactic body radiation therapy.

BACKGROUND: In single-isocenter multitarget stereotactic body radiotherapy (SBRT), geometric miss risks arise from uncertainties in intertarget position. However, its assessment is inadequate, and may be interfered by the reconstructed tumor position errors (RPEs) during simulated CT and cone beam CT (CBCT) acquisition. This study aimed to quantify intertarget position variations and assess factors influencing it. METHODS: We analyzed data from 14 patients with 100 tumor pairs treated with single-isocenter SBRT. Intertarget position variation was measured using 4D-CT simulation to assess the intertarget position variations (ΔD) during routine treatment process. Additionally, a homologous 4D-CBCT simulation provided RPE-free comparison to determine the impact of RPEs, and isolating purely tumor motion induced ΔD to evaluate potential contributing factors. RESULTS: The median ΔD was 4.3 mm (4D-CT) and 3.4 mm (4D-CBCT). Variations exceeding 5 mm and 10 mm were observed in 31.1% and 5.5% (4D-CT) and 20.4% and 3.4% (4D-CBCT) of fractions, respectively. RPEs necessitated an additional 1-2 mm safety margin. Intertarget distance and breathing amplitude variability showed weak correlations with variation (Rs = 0.33 and 0.31). The ΔD differed significantly by locations (upper vs. lower lobe and right vs. Left lung). Notably, left lung tumor pairs exhibited the highest risk. CONCLUSIONS: This study provide a reliable way to assess intertarget position variation by using both 4D-CT and 4D-CBCT simulation. Consequently, single-isocenter SBRT for multiple lung tumors carries high risk of geometric miss. Tumor motion and RPE constitute a substantial portion of intertarget position variation, requiring correspondent strategies to minimize the intertarget uncertainties.

FTO alleviated ferroptosis in septic cardiomyopathy via mediating the m6A modification of BACH1.

Sepsis is a global health challenge that results in systemic inflammation, oxidative stress, and multi-organ dysfunction, with the heart being particularly susceptible. This study aimed to elucidate the effect of FTO, a key regulator in m6A methylation in septic cardiomyopathy, and its potential therapeutic implications. Cellular and animal models of septic myocardial injury were established. Moreover, it was revealed that ferroptosis, which is a form of programmed necrosis occurring with iron dependence, was activated within cardiomyocytes during septic conditions. The overexpression of FTO-suppressed ferroptosis alleviated heart inflammation and dysfunction and improved survival rates in vivo. However, the protective effects of FTO were attenuated by the overexpression of BACH1, which is a molecule negatively correlated with FTO. Mechanistically, FTO modulated the m6A modification of BACH1, suggesting a complex interplay in the regulation of cardiomyocyte damage and sepsis. Our findings reveal the potential of targeting the FTO/BACH1 axis and ferroptosis inhibitors as therapeutic strategies for sepsis-induced cardiac injuries.

Biomass Chitosan-Based Tubular/Sheet Superhydrophobic Aerogels Enable Efficient Oil/Water Separation.

Water pollution, which is caused by leakage of oily substances, has been recognized as one of the most serious global environmental pollutions endangering the ecosystem. High-quality porous materials with superwettability, which are typically constructed in the form of aerogels, hold huge potential in the field of adsorption and removal of oily substances form water. Herein, we developed a facile strategy to fabricate a novel biomass absorbent with a layered tubular/sheet structure for efficient oil/water separation. The aerogels were fabricated by assembling hollow poplar catkin fiber into chitosan sheets using a directional freeze-drying method. The obtained aerogels were further wrapped with -CH3-ended siloxane structures using CH3SiCl3. This superhydrophobic aerogel (CA ≈ 154 ± 0.4°) could rapidly trap and remove oils from water with a large sorption range of 33.06-73.22 g/g. The aerogel facilitated stable oil recovery (90.07-92.34%) by squeezing after 10 sorption-desorption cycles because of its mechanical robustness (91.76% strain remaining after 50 compress-release cycles). The novel design, low cost, and sustainability of the aerogel provide an efficient and environmentally friendly solution for handling oil spills.

Site-Selective, Multistep Functionalizations of CO2-Based Hyperbranched Poly(alkynoate)s toward Functional Polymetric Materials.

Hyperbranched polymers constructed from CO2 possess unique architectures and properties; however, they are difficult to prepare. In this work, CO2-based, hyperbranched poly(alkynoate)s (hb-PAs) with high molecular weights and degrees of branching are facilely prepared under atmospheric pressure in only 3 h. Because hb-PAs possess two types of ethynyl groups with different reactivities, they can undergo site-selective, three-step functionalizations with nearly 100% conversion in each step. Taking advantage of this unique feature, functional hb-PAs with versatile properties are constructed that could be selectively tailored to contain hydrophilic oligo(ethylene glycol) chains in their branched chains, on their periphery, or both via tandem polymerizations. Hyperbranched polyprodrug amphiphiles with high drug loading content (44.3 wt%) are also generated, along with an artificial light-harvesting system with high energy transfer efficiency (up to 92%) and white-light-emitting polymers. This work not only provides an efficient pathway to convert CO2 into hyperbranched polymers, but also offers an effective platform for site-selective multistep functionalizations toward functional polymeric materials.

Enhanced production of unusual triterpenoids from Kadsura angustifolia fermented by a symbiont endophytic fungus, Penicillium sp. SWUKD4.1850.

Highly oxygenated schitriterpenoids are interesting for study of their structures, bioactivities and synthesis. From Kadsura angustifolia fermented by an associated symbiotic endophytic fungus, Penicillium sp. SWUKD4.1850, nine undescribed triterpenoids, kadhenrischinins A-H, and 7ß-schinalactone C together with four known triterpenoids, henrischinins A and B, schinalactone C and nigranoic acid were isolated and established by the extensive 1D-, 2D-NMR, HR-ESI-MS and ECD data analysis. Except nigranoic acid, all these metabolites have been first detected in non-fermented K. angustifolia. Structurally, kadhenrischinins A-D belong to the relatively rare class of highly oxygenated schitriterpenoids that contain a unique 3-one-2-oxabicyclo [3,2,1]-octane motif, while kadhenrischinins E-H feature a cyclopentane ring in a side chain rarely found in the family Schisandraceae. These results indicated that fermentation of K. angustifolia with SWUKD4.1850 induced the production of highly oxygenated schitriterpenoids from nigranoic acid, which provided a guidance to obtain desired compounds from those plants initially thought not to produce. This is the first report on the fermentation of K. angustifolia medical plant and the first discovery of highly oxygenated schitriterpenoids by microbial technology.

Switch regulation of interleukin-1 beta in downstream of inflammatory cytokines induced by two micro-sized silica particles on differentiated THP-1 macrophages.

To investigate the regulated role of IL-1ß in initiating and maintaining inflammation, PMA-differentiated THP-1 macrophages were exposed to two micro-sized crystalline silica particles (Si3-5µm and Si1µm) from 3h to 24h, respectively. Cytotoxicity and inflammatory cytokines (IL-1ß, TNF-α and IL-6) expressions measured showed that they were induced by both silica particles in positive dose-dependent manners. The levels of inflammatory cytokines induced by Si1µm were higher than those induced by Si3-5µm at low concentration. When pretreated with anti-human IL-1ß, not only the high levels of IL-1ß but also elevated TNF-α and IL-6 induced by both silica particles were remarkably blocked, especially Si1µm particle. In addition, recombinant human IL-1ß protein could induce macrophages to strikingly augment TNF-α and IL-6 expressions. Our data suggest that IL-1ß could play a critical role of switching regulation in the downstream inflammation induced by micro-sized silica particles.

Particle-size-dependent cytokine responses and cell damage induced by silica particles and macrophages-derived mediators in endothelial cell.

Epidemiological evidence reports silica dust exposure has been associated with increased risk of cardiovascular diseases, but the mechanisms are largely unknown. In this study, endothelial cells were exposed to increasing concentrations of two sizes silica particles and the soluble mediators released by macrophages treated with the same particles for 24 h. Expression and release of cytokines (IL-1ß, TNF-α and IL-6) were measured by using ELISA. Cytotoxicity was measured by MTT assay and LDH release. We show that both ways induced increases in cell toxicity and cytokines in a dose-dependent manner. For smaller particles, the soluble mediators are more capable of increasing cytokines compared with the effect of particles directly. For larger particles, evaluating results of these two ways are similar. Either way, smaller particles make the increasing action of cell toxicity and cytokines more remarkable. Our results indicate both silica particle and macrophage-derived mediators can induce endothelial cell injury and inflammation and demonstrate the potential importance of the particle sizes in this effect.

[The role of interleukin-1ß on the pulmonary fibrosis in mice exposed to crystalline silica].

OBJECTIVE: This study was designed to evaluate the role of interleukin (IL)-1ß in the development of fibrosis in mice exposed to silica. METHODS: The total of 96 Male C57BL/6 mice were divided into four groups. (1) blank control group, (2) PBS group in which mice were instilled with PBS only, (3) silica + IL-1ß mAb group in which mice were instilled with 2.5 mg silica dust and 40 µg anti-IL-1ß mAb, (4) silica group in which mice were instilled with 2.5 mg silica dust and 40 µg IgG. The final volume of suspension or PBS instilled into the mouse was 50 µl. At 7, 28 and 84 days after treatment, 8 mice were sacrificed in each group. Then BALF was collected for the count of inflammatory cells and cytokines determination. The lung tissues were collected for the detecting of mRNA levels of fibrogenic molecules. RESULTS: The collagen deposition induced by silica in the lung tissues was partly inhibited by anti-IL-1ß. A intensely pulmonary cytokines such as IL-1ß, TNF-α, MCP-1 were induced by crystalline silica exposure, and partly inhibited by anti-IL-1ß. The levels of TGF-ß and fibronectin in silica exposed mice were significantly elevated than those in control mice at days 28 and 84 after treatment (P < 0.01). And the mRNA levels of TGF-ß, collagen I and fibronectin were significantly decreased in silica+IL-1ß mAb group when compared with those in silica group at days 7, 28 and 84 (P < 0.01). There was a significant decrease of the ratios of IFN-γ/IL-4 in both silica+anti-IL-1ß mAb and silica groups when compared with those in control mice at the above three time points (P < 0.01). However, the IFN-γ/IL-4 ratios in silica+anti-IL-1ß group were significantly higher than those in silica group at 7, 28 and 84 days (P < 0.05 or P < 0.01). CONCLUSION: IL-1ß may promote the pulmonary fibrosis in mice exposed to silica.

Neutralization of interleukin-1 beta attenuates silica-induced lung inflammation and fibrosis in C57BL/6 mice.

The inflammation and fibrosis induced by silica dust are considered to be substantial responses in silicosis progression. Interleukin-1 beta (IL-1ß) plays an important role in silica-induced lung inflammation, but the mechanisms that underlie the influence of IL-1ß on the progression of silicosis remain unclear. In this study, the role of IL-1ß in silica-induced inflammation and fibrosis was evaluated by administering a suspension of 2.5-mg silica dust, either with or without 40 µg anti-mouse IL-1ß monoclonal antibody (mAb), to the lungs of male C57BL/6 mice. Silica + anti-IL-1ß mAb-treated mice showed the depletion of IL-1ß as well as the attenuation of inflammation, as evaluated in the bronchoalveolar lavage fluid (BALF) and histological sections from 1 to 84 days after silica exposure. Further study of the BALF indicated that inhibition of IL-1ß could reduce the contents of tumor necrosis factor-alpha and monocyte chemoattractant protein-1. The real-time PCR and pathology results showed that the neutralization of IL-1ß attenuated silica-induced fibrosis by inhibiting the gene expression of transforming growth factor-beta 1, collagen I and fibronectin. The examination of Th1-cytokine and Th2-cytokine suggested that depletion of IL-1ß decelerated the Th1/Th2 balance toward a Th2-dominant response. In conclusion, the present study suggests that the neutralization of IL-1ß attenuates silica-induced inflammation and fibrosis by inhibiting other inflammatory and fibrogenic mediators and modulating the Th1/Th2 balance.

Association between proinflammatory responses of respirable silica dust and adverse health effects among dust-exposed workers.

OBJECTIVE: To evaluate proinflammatory responses induced by respirable silica dust samples and to analyze the role of those responses in explaining adverse health effects among dust-exposed workers in pottery factoryies and tungsten and tin mines. METHODS: Proinflammatory cytokines of cells were determined after being treated with silica dust samples. Adverse health effects of workers were calculated on the basis of a cohort study. RESULTS: Incidence and mortality of silicosis among tungsten miners were higher than those in other workers. The incidence of interleukin-1ß levels was highest in tungsten mines, which was consistent with the incidence of silicosis in tungsten miners. The higher levels of TNF-α and interleukin-6 released from macrophages might be helpful in explaining increased mortalities from lung cancer among tin miners. CONCLUSIONS: Interleukin-1ß could be a sensitive biomarker in predicting fibrogenic potential of silica dust and the risk of silicosis among dust-exposed workers.