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Background The impact of beam dosimetry changes brought on by target degradation has not been well investigated. Purpose To determine the optimal dosimetry metrics for detecting target degradation and to investigate the impact of beam dosimetry changes brought on by target degradation. Methods The EGSnrc Monte Carlo programs were used to model the Varian Novalis Tx linear accelerator. By altering the central portion of the photon target with a cylindrical vacuum zone, few target degradation scenarios were simulated and compared with the nominal condition. For square photon beams defined by the jaws, the effects of target degradation on beam output, beam quality (percentage depth dose, PDD), beam profile (off‐axis factor), relative output factor (ROF), and wedge factor (WF) were examined. Few degradation scenarios were used to retroactively model the effects on patient‐specific quality assurance (PSQA). Results Under the realistic degradation conditions (0.6–0.7 mm depth, 1.0–2.0 mm widths), the 6MV beam output decreased by 5.7%–24.1% and the 30 cm field diagonal profile sag in the horns by a max deviation of 3.8%–5.9%, however, the PDD20,10 varied within 1%, and the flatness deviated by 0.74%–1.35%, respectively. As the photon target got more degraded, the beam output, beam quality and profile showed a downgrade trend from the baseline. The PDD20,10 varied from 0.7% to ‐2.8% in the 10 cm field. Before the target degraded with a 2 mm width and 0.889 mm depth hole, ROF and WF were stable (within 2% deviation). The pelvic case gamma result showed obvious decrease (90.9%) under degradation depth 0.7 mm and width 2.0 mm. Conclusion A technical approach was created and verified for precise Monte Carlo simulation of linear accelerator target degradation scenarios. The parameters with the highest sensitivity for detecting target degradation were beam output and large field diagonal profile deviation in the 0.95 field size range.

Purpose The positional accuracy of MLC is an important element in establishing the exact dosimetry in VMAT. We comprehensively analyzed factors that may affect MLC positional accuracy in VMAT, and constructed a model to predict MLC positional deviation and estimate planning delivery quality according to the VMAT plans before delivery. Methods A total of 744 “dynalog” files for 23 VMAT plans were extracted randomly from treatment database. Multi‐correlation was used to analyzed the potential influences on MLC positional accuracy, including the spatial characteristics and temporal variability of VMAT fluence, and the mechanical wear parameters of MLC. We developed a model to forecast the accuracy of MLC moving position utilizing the random forest (RF) ensemble learning method. Spearman correlation was used to further investigate the associations between MLC positional deviation and dosage deviations as well as gamma passing rates. Results The MLC positional deviation and effective impact factors show a strong multi‐correlation (R = 0.701, p‐value < 0.05). This leads to the development of a highly accurate prediction model with average variables explained of 95.03% and average MSE of 0.059 in the 5‐fold cross‐validation, and MSE of 0.074 for the test data was obtained. The absolute dose deviations caused by MLC positional deviation ranging from 12.948 to 210.235 cGy, while the relative volume deviation remained small at 0.470%–5.161%. The average MLC positional deviation correlated substantially with gamma passing rates (with correlation coefficient of −0.506 to −0.720 and p‐value < 0.05) but marginally with dosage deviations (with correlation coefficient < 0.498 and p‐value > 0.05). Conclusions The RF predictive model provides a prior tool for VMAT quality assurance.

Amyloid-like assembly is not only associated with pathological events, but also leads to the development of novel nanomaterials with unique properties. Herein, using Fmoc diphenylalanine peptide (Fmoc–F–F) as a minimalistic model, we found that histidine can modulate the assembly behavior of Fmoc–F–F and induce enzyme-like catalysis. Specifically, the presence of histidine rearranges the β structure of Fmoc–F–F to assemble nanofilaments, resulting in the formation of active site to mimic peroxidase-like activity that catalyzes ROS generation. A similar catalytic property is also observed in Aβ assembled filaments, which is correlated with the spatial proximity between intermolecular histidine and F-F. Notably, the assembled Aβ filaments are able to induce cellular ROS elevation and damage neuron cells, providing an insight into the pathological relationship between Aβ aggregation and Alzheimer’s disease. These findings highlight the potential of histidine as a modulator in amyloid-like assembly of peptide nanomaterials exerting enzyme-like catalysis. In this work, the authors report that Histidine residues play a critical role in modulating amyloid-like assembly and building active sites for Fmoc–F–F and Aβ aggregates. Aβ1-42 filaments were found to perform peroxidase-like activity to enhance oxidative stress, which might also be ascribed to the interaction mode of His and F-F.

The innovations of agricultural production and their extensive dispersal promoted the transformation of human livelihoods and profoundly influenced the evolution of human-land relationships in late prehistoric Eurasia. The Steppe and Silk Roads (SSRs) played important roles in the transcontinental exchange and dispersal of cereal crops and livestock related to agricultural innovation across Eurasia before the Han Dynasty (202 BC to AD 220), while the geographical-temporal variations in prehistoric subsistence in relation to the spread and exchange of cereal crops and livestock originating from different areas of Eurasia still remain unclear. In this paper, we explore these issues based on the review and analysis of published archaeobotanical, zooarchaeological, and carbon-stable isotope data from human bones from Neolithic-Early Iron Age sites in areas along the SSRs, with a comparison to updated results based on radiocarbon dating and ancient DNA analyses. Our results suggest that humans engaged in hunting game, while foxtail/broomcorn millet cultivation gradually became the primary subsistence strategy in Eastern SSRs from 10,500 to 6000 a BP. In contemporaneous Western SSRs, humans mainly cultivated wheat/barley and raised sheep/goats, cattle, and pigs. Trans-Eurasian exchange, which is reflected by the mixed utilization of wheat/barley and millet, emerged in the south-central Steppe during 6000–4000 a BP, while millet cultivation and pig husbandry became the dominant livelihoods in most areas of Eastern SSRs. During 4000–2200 a BP, Silk Roads became the major passageway for trans-Eurasian exchange, the interactive development of oasis agriculture and pastoralism facilitated intensive human settlement in the Central Silk Roads, and subsistence strategies substantially changed with significant geographical differences in Eastern SSRs, while subsistence in some areas of Western SSRs was evidently affected by the introduction and adoption of millet crops after 3000 a BP. The geographical-temporal variations in subsistence in the SSRs from the Neolithic to Early Iron Age were primarily affected by the prehistoric dispersal of farming groups across Eurasia, which was accompanied by the spread of cereal crops/livestock, while the impacts of climate change still need to be further evaluated.

The concept of niche similarity is crucial for understanding species invasions. An in-depth understanding of different niches can aid in developing effective control strategies, not only at the community level but also in population interactions. In this study, we investigated the invasion of Spartina alterniflora in China by selecting nine major mangrove species along the Chinese coast. Utilizing an ensemble species distribution model (ESDM), we compared the niche characteristics of these mangroves with S. alterniflora . We found that S. alterniflora has a broad latitudinal adaptability (39.22–21.67˚N), significantly greater than the mangroves. Excoecaria agallocha has the largest potential distribution area (74,729 km 2 ), while Kandelia obovata shows the widest climatic adaptability (latitude: 30.85˚N to 18.19˚N). The ecological niches of the mangroves and S. alterniflora overlap (D.overlap: 0.015–0.254, Niche similarity index: 0.044–0.551), driven by different species-specific factors. K. obovata and S. alterniflora have the highest niche similarity due to the similarities in precipitation during the driest month and precipitation seasonality. Overall, mangroves in China are vulnerable to invasion by S. alterniflora . Strengthening mangrove protection is essential for their healthy development, especially under frequent extreme weather conditions, with a focus on protecting K. obovata .

Apatinib, an inhibitor of vascular endothelial growth factor receptor-2, has been shown to promote anti-cancer action across a wide range of malignancies, including gastric, lung, and breast cancers. Our previous study showed that apatinib increases apoptosis in anaplastic thyroid carcinoma (ATC), but the direct functional mechanism of tumor lethality mediated by apatinib is still unknown. In this study, we demonstrated that apatinib induced both autophagy and apoptosis in human ATC cells through downregulation of p-AKT and p-mTOR signals via the AKT/mTOR pathway. Moreover, inhibition of apatinib-induced autophagy increased apatinib-induced apoptosis in ATC cells, and additional tumor suppression was critically produced by the combination of apatinib and the autophagy inhibitor chloroquine in vivo and in vitro. These findings showed that both autophagy and AKT/mTOR signals were engaged in ATC cell death evoked by apatinib. ATC patients might benefit from the new anti-cancer drug, and molecular targeted treatment in combination with autophagy inhibitors shows promise as a treatment improvement.

The Proto-Shang, the Shang and the Zhou dynasties (∼2000-221 BCE: Before Common Era) are key periods in the origin and evolution of ancient civilizations in China since the periods include the processes and mechanisms of social development in the Central Plains of China during the Bronze Age. However, human-environment interactions in the context of trans-Eurasia cultural exchange during that time are not well-understood. In this study, isotopic analysis and radiocarbon dating of human and animal bones from Xinancheng cemetery in southeast Shanxi Province are reported. It was deduced that, for the period ∼1000-800 BCE, humans buried in Xinancheng cemetery relied primarily on C4-based foods and upper-status individuals consumed more animal protein and probably C3 crops. Also, considering the paleoclimate and other archaeological data of the Central Plains, the human diet and subsistence strategies changed significantly with more C3 staples such as wheat being consumed during the Eastern Zhou (770-221 BCE), as evidenced by an increased intake of wheat by lower-status individuals and the development of a mixed wheat and millet agricultural system. It is argued that the socio-economic change around the late western Zhou-early eastern Zhou Dynasty occurred as a result of the necessity to adapt to the aggravation caused by climate deterioration and population pressures, factors which profoundly influenced the economic and lifestyle patterns in ancient China. The socio-economic system of the Eastern Zhou Dynasty displayed more resilience to climate change than that of earlier periods.

Diet has emerged as a key impact factor for gut microbiota function. However, the complexity of dietary components makes it difficult to predict specific outcomes. Here we investigate the impact of plant-derived nanoparticles (PNP) on gut microbiota and metabolites in context of cancer immunotherapy with the humanized gnotobiotic mouse model. Specifically, we show that ginger-derived exosome-like nanoparticle (GELN) preferentially taken up by Lachnospiraceae and Lactobacillaceae mediated by digalactosyldiacylglycerol (DGDG) and glycine, respectively. We further demonstrate that GELN aly-miR159a-3p enhances anti-PD-L1 therapy in melanoma by inhibiting the expression of recipient bacterial phospholipase C (PLC) and increases the accumulation of docosahexaenoic acid (DHA). An increased level of circulating DHA inhibits PD-L1 expression in tumor cells by binding the PD-L1 promoter and subsequently prevents c-myc-initiated transcription of PD-L1. Colonization of germ-free male mice with gut bacteria from anti-PD-L1 non-responding patients supplemented with DHA enhances the efficacy of anti-PD-L1 therapy compared to controls. Our findings reveal a previously unknown mechanistic impact of PNP on human tumor immunotherapy by modulating gut bacterial metabolic pathways. The impact of diet on gut microbiota and metabolites in context of cancer immunotherapy remains elusive. Here the authors reveal ginger-derived exosome-like nanoparticle (GELN) aly-miR159a-3p enhances anti-PD-L1 therapy by increasing microbiota-dependent docosahexaenoic acid (DHA) level thus limiting tumor cell PD-L1 expression.

Gastric cancer is the fifth most common cancer worldwide and Hippo-Yap is the novel signaling pathway which plays an important role in gastric cancer tumor development and progression. However, little insight is available to date regarding the specific role of Yes-associated protein (Yap) in gastric cancer. In the present study, we identified the mechanism through which Yap sustains gastric cancer viability and migration. Yap was greatly upregulated in gastric cancer cells and its expression promoted cellular migration and survival. Functional studies found that knockdown of Yap reduced the mitophagy activity, which subsequently caused mitochondrial apoptosis and cellular oxidative stress. The latter impaired adhesive protein expression, alleviated F-actin expression, blunted lamellipodium formation, leading to inhibition of cancer cell motility. Mechanistically, Yap preserved Sirtuin 1 (SIRT1) activity which manipulated mitofusin 2 (Mfn2) expression and subsequent mitophagy. Loss of Yap reduced SIRT1 expression and inhibited Mfn2-mediated mitophagy. Collectively, our results identified Hippo-Yap as a tumor promoter in gastric cancer that was mediated via activation of the SIRT1/Mfn2/mitophagy axis, with potential applications to gastric cancer therapy involving cancer survival and migration.

Curcumin (CUR) is a hydrophobic polyphenol from turmeric with various biological activities. However, its poor water solubility limits its application in food and pharmaceutical fields. Here, the curcumin and mogroside (MOG) self‐assembled nanoparticles (CUR–MOG NPs) with well water solubility were successfully prepared. The CUR–MOG NPs were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), x‐ray diffraction (XRD), UV‐visible spectrophotometer, Fourier transform infrared (FTIR) spectroscopy, and thermogravimetric analysis (TGA). The antioxidant activity and HepG2 cell cytotoxicity were further evaluated. CUR–MOG NPs exhibited a particle size of 59.96 ± 0.852 nm with a polydispersity coefficient of 0.077 ± 0.013. The CUR encapsulation efficiency of CUR–MOG NPs was 86.35 % ± 0.877 % . The XRD, UV‐visible spectrophotometer, FTIR, and TGA confirmed that the π – π stacking, hydrophobic interaction, and hydrogen bonding may contribute to the successfully formed self‐assembled nanoparticles. Moreover, nanoparticles had significantly enhanced the water solubility of CUR, increasing from 10.7 ng/mL in pure CUR to 1.135 mg/mL in CUR–MOG NPs. The CUR–MOG NPs demonstrated comparable DPPH radical scavenging activity and HepG2 cell cytotoxicity with those of free CUR. CUR–MOG NPs exhibited a superior water‐soluble capability, which may serve as a promising system for improving its applications in food and pharmaceutical products.