Rapid Selection of Patients Suitable for Deep Inspiration Breath-Hold Using an Automatic Delineating System and RapidPlan Model in Left Breast Cancer Patients undergoing Adjuvant Radiotherapy with IMRT.

PURPOSE: This study aimed to determine whether radiotherapy plans created using an automatic delineating system and a RapidPlan (RP) module could rapidly and accurately predict heart doses and benefit from deep inspiratory breath-hold (DIBH)in left breast cancer patients. METHODS AND MATERIALS: One hundred thirty-six clinically approved free breathing (FB) plans for patients with left breast cancer were included, defined as manual delineation-manual plan (MD-MP). A total of 104/136 plans were selected for RP model training. A total of 32/136 patients were automatically delineated by software, after which the RP generated plans, defined as automatic delineation-RapidPlan (AD-RP). In addition, 40 patients who used DIBH were included to analyze differences in heart benefits from DIBH. RESULTS: Two RP models were established for post breast-conserving surgery (BCS) and post modified radical mastectomy (MRM). There were no significant differences in most of the dosimetric parameters between the MD-MP and AD-RP. The heart doses of the two plans were strongly correlated in patients after BCS (0.80 ≤ r ≤ 0.88, P < 0.05) and moderately correlated in patients after MRM (0.46 ≤ r ≤ 0.58, P < 0.05). The RP model predicted the mean heart dose (MHD) within ± 59.67 cGy and ± 63.32 cGy for patients who underwent the two surgeries described above. The heart benefits from DIBH were significantly greater in patients with FB-MHD ≥ 4 Gy than in those with FB-MHD < 4 Gy. CONCLUSIONS: The combined automatic delineation RP model allows for the rapid and accurate prediction of heart dose under FB in patients with left breast cancer. FB-MHD ≥ 4 Gy can be used as a dose threshold to select patients suitable for DIBH.

What drives the changing characteristics of phytoplankton in urban lakes: Climate, hydrology, or human disturbance?

Phytoplankton in shallow urban lakes are influenced by various environmental factors. However, the long-term coupling effects and impact pathways of these environmental variables on phytoplankton remain unclear. This is an emerging issue due to high urbanization and the resultant complex climate, lake hydrology and morphology, human interference, and water quality parameter changes. This study used Tangxun Lake, the largest urban lake in the Yangtze River Economic Belt, as an example to assess for the first time the individual contributions and coupled effects of four environmental variables and fourteen indicators on chlorophyll-a (Chla) concentrations under two scenarios from 2000 to 2019. Additionally, the influence pathways between the environmental variables and Chla concentration were quantified. The results indicated that the Chla concentration was most affected by lake hydrology and morphology, as were the total nitrogen, total phosphorus, and transparency. Especially after urbanization (2015-2019), the coupling effect of human interference, lake hydrology and morphology, and water quality parameters was strongest (18%). This is mainly due to fluctuations in the lake water level and an increase in the shape index of lake morphology, large amounts of nutrients were input, which reduced lake transparency and indirectly changed the Chla content. In addition, due to the rapid development of Wuhan city, the expansion of construction land has led to an increase in impervious surface area and a decrease in lake area. During periods of intense summer rainfall, a substantial amount of pollutants entered the lakes through surface runoff, resulting in decreased lake transparency, and elevated concentrations of nitrogen and phosphorus, indirectly increasing the Chla content. This study provides a scientific basis for aquatic ecological assessment and pollution control in urban shallow lakes.

The divergence between potential and actual evapotranspiration: An insight from climate, water, and vegetation change.

Recently, unprecedented extreme drought has appeared around the world. As the most direct signal of drought, evapotranspiration deserves a more systematic and comprehensive study. Further depicting their divergence of potential (ETp) and actual evapotranspiration (ETa) will help to explore the limitation of evapotranspiration. In this paper, the multi-source remote sensing datasets from the Climate Research Unit (CRU), Gravity Recovery and Climate Experiment (GRACE) and its follow-on experiment (GRACE-FO), the Global Land Data Assimilation System (GLDAS), and the Moderate Resolution Imaging Spectroradiometer (MODIS) during 2002 to 2020 were employed to explore the influence of meteorological, hydrological and botanical factors on ETp, ETa and their divergence - reduction of evapotranspiration (Er) which represents regional vegetation and water limitations. According to the Pearson correlation analysis and the Boruta Algorithm based on Random Forest, the temperature is the first decisive promoter of evapotranspiration in the most area while the sparse vegetation is the primary or second determinant limiting the evapotranspiration in 61.84% of the world. In addition, the Coupled Model Intercomparison Project (CMIP6) data from 2030 to 2090 and the support vector machine regression (SVMR) model were applied to predict the future global ETp, ETa and Er on the pixel scale. Predicted results of the model considering the water change not only can highly improve the model performance (with higher R2), but also can simulate the drought in Europe and the more intense ETa in Africa. Thus, Er proposed in this study provide a good reference for regional ETa except for ETp. The future evapotranspiration value derived by introducing the water storage changes into the machine learning model in this study is also valuable for climate change adaptation and drought warning.

N6-methyladenine- induced LINC00667 promoted breast cancer progression through m6A/KIAA1429 positive feedback loop.

Increasing evidence supports that N6-methyladenine (m6A) and long noncoding RNAs (lncRNAs) both act as master regulators involved in breast cancer (BC) tumorigenesis at epigenetic modification level. Here, our research tries to unveil the interaction of m6A and lncRNAs on BC progression and explore the underlying regulatory mechanism. In the current study, we found that LINC00667 was m6A-modified lncRNA, which was up-regulated upon the overexpression of KIAA1429. The high expression of LINC00667 was correlated with the prognosis of BC patients. Bio-functional assays indicated that LINC00667 promoted the proliferation and migration of BC cells. Mechanistic assays illustrated that KIAA1429 targeted the m6A modification site of LINC00667 and enhanced its mRNA stability. Moreover, LINC00667 positively regulated the KIAA1429 via sponging miR-556-5p, forming a KIAA1429/m6A/LINC00667/miR-556-5p feedback loop. Collectively, the central findings of our study suggest that KIAA1429-induced LINC00667 exerted its functions as an oncogene in BC progression through m6A-dependent feedback loop.

Endothelial cell-derived SSAO can increase MLC20 phosphorylation in VSMCs.

Vascular hyporesponsiveness in the shock decompensation period is an important factor leading to death. Myosin light chain 20 (MLC20) is the main effector protein that regulates vascular reactivity. However, whether the change in semicarbazide-sensitive amine oxidase (SSAO) expression during hypoxia can change the MLC20 phosphorylation level, and its underlying mechanism were not clear. The amine oxidase copper containing 3 (AOC3) overexpressing adenovirus vector was constructed and transfected into rat intestinal microvascular endothelial cells (RIMECs) to overexpress SSAO, and the RIMECs were co-cultured with rat intestinal microvascular smooth muscle cells (RIMSCs). The changes in SSAO/inducible nitric oxide synthase (iNOS)/Rho associate coiled-coil containing protein kinase 1 (ROCK1) expression levels and MLC20 phosphorylation level were detected. Here we found that the increased SSAO by AOC3 overexpression can decrease the iNOS expression level and its activity after hypoxia. In addition, RIMSCs co-cultured with RIMECs overexpressed with AOC3 gene had significantly higher ROCK1 protein level and MLC20 phosphorylation level than RIMSCs co-cultured with normal RIMECs. Our study demonstrated that SSAO overexpression can significantly inhibit iNOS activity, promote RhoA/ROCK pathway activation, and increase the phosphorylation level of MLC20, which might be the potential mechanism in relieving the vascular hyporesponsiveness during shock decompensation.

Functions and clinical significance of KLRG1 in the development of lung adenocarcinoma and immunotherapy.

BACKGROUND: As a marker of differentiation, Killer cell lectin like receptor G1 (KLRG1) plays an inhibitory role in human NK cells and T cells. However, its clinical role remains inexplicit. This work intended to investigate the predictive ability of KLRG1 on the efficacy of immune-checkpoint inhibitor in the treatment of lung adenocarcinoma (LUAD), as well as contribute to the possible molecular mechanisms of KLRG1 on LUAD development. METHODS: Using data from the Gene Expression Omnibus, the Cancer Genome Atlas and the Genotype-Tissue Expression, we compared the expression of KLRG1 and its related genes Bruton tyrosine kinase (BTK), C-C motif chemokine receptor 2 (CCR2), Scm polycomb group protein like 4 (SCML4) in LUAD and normal lung tissues. We also established stable LUAD cell lines with KLRG1 gene knockdown and investigated the effect of KLRG1 knockdown on tumor cell proliferation. We further studied the prognostic value of the four factors in terms of overall survival (OS) in LUAD. Using data from the Gene Expression Omnibus, we further investigated the expression of KLRG1 in the patients with different responses after immunotherapy. RESULTS: The expression of KLRG1, BTK, CCR2 and SCML4 was significantly downregulated in LUAD tissues compared to normal controls. Knockdown of KLRG1 promoted the proliferation of A549 and H1299 tumor cells. And low expression of these four factors was associated with unfavorable overall survival in patients with LUAD. Furthermore, low expression of KLRG1 also correlated with poor responses to immunotherapy in LUAD patients. CONCLUSION: Based on these findings, we inferred that KLRG1 had significant correlation with immunotherapy response. Meanwhile, KLRG1, BTK, CCR2 and SCML4 might serve as valuable prognostic biomarkers in LUAD.