Evaluate the value of prolonging the duration of tiopronin for injection administration in preventing hepatotoxicity

Abstract As part of supportive therapy, prophylaxis with tiopronin for injection (TI) against common hepatotoxicity complications has often been used. However, methods to prevent hepatotoxicity have not been established. Therefore, our study was aimed to find out the relationship between the periods of TI prophylaxis and post-treatment hepatotoxicity, and evaluated the value of prolonging the duration of TI administration in preventing hepatotoxicity. Hepatotoxicity was detected through liver transaminases, bilirubin, alkaline phosphatase, and clinical features of liver insufficiency. Multivariable logistic regressions were conducted to examine the association of the periods of TI prophylaxis and post-treatment hepatotoxicity. Between January 2022 and March 2023, a total of 452 patients with gynecological cancer were enrolled in the study, of which 93 (20.58%) participants were post-treatment hepatotoxicity positive. TI with different prevention days were no significant difference among participants with or without post-treatment hepatotoxicity in crude model (P > 0.05). The P-value, the odds ratios (OR) and 95% confidence intervals (CI) of participants with TI prophylaxis for 1 day for post-treatment hepatotoxicity were 0.040, 3.534 (1.061–11.765) in fully adjusted model. Past history of hepatotoxicity is a confounding variable, and there was no significant difference for post-treatment hepatotoxicity when stratified by past history of hepatotoxicity (P > 0.05). The study indicate that the periods of TI prophylaxis is not associated with post-treatment hepatotoxicity, suggesting that prolonged the periods of TI prophylaxis might be an invalid method for the prevention of post-treatment hepatotoxicity

Reconfigurable Intelligent Surfaces: Principles and Opportunities

International audienceReconfigurable intelligent surfaces (RISs), also known as intelligent reflecting surfaces (IRSs), or large intelligent surfaces (LISs) 1 , have received significant attention for their potential to enhance the capacity and coverage of wireless networks by smartly reconfiguring the wireless propagation environment. Therefore, RISs are considered a promising technology for the sixth-generation (6G) of communication networks. In this context, we provide a comprehensive overview of the state-of-the-art on RISs, with focus on their operating principles, performance evaluation, beamforming design and resource management, applications of machine learning to RIS-enhanced wireless networks, as well a

Spring Wheat–Summer Maize Annual Crop System Grain Yield and Nitrogen Utilization Response to Nitrogen Application Rate in the Thermal–Resource–Limited Region of the North China Plain

Spring wheat–summer maize (SWSM) annual crop systems were formed to satisfy the maize grain mechanized harvest thermal requirement in the thermal–resource–limited region of the North China Plain. However, the nitrogen (N) application rate effect on SWSM annual yield formation, N accumulation and utilization were barely evaluated. Two–year field experiments were conducted to evaluate the effects of the N application rate on the annual yield of SWSM, observe N accumulation and utilization, and identify the optimized N application. The experiments were conducted under 5 N levels of 0 (N0), 180 (N180), 240 (N240), 300 (N300), and 360 (N360) kg ha−1. The results showed that spring wheat, summer maize and annual cereal yield under the N240 and N480 treatments obtained the highest grain yield (GY) of 5038, 1282 and 16,320 kg ha−1, respectively, and the optimal N application rate was estimated using a linear–plateau model to be 231–307, 222–337 and 463–571 kg ha−1 with maximum GY of 4654–5317, 11,727–12,003 and 16,349–16,658 kg ha−1, respectively. With the increase in the N application rate, the dry matter accumulation (DM) were significantly increased by 16.9–173.5% for spring wheat and 11.1≈–76.8% for summer maize, respectively; and the annual cereal DM was 15.1–179.7% greater than that with N0 treatment, respectively. Spring wheat, summer maize and the annual cereal total N accumulation (TN) under N360 and N720 treatments were significantly increased by 5.4–19.1%, 16.6–32.3% and 11.5–26.2%, respectively, compared to the other treatments; however, N use efficiency for biomass and grain production (NUEbms and NUEg) were decreased significantly by 10.9–13.6% and 8.9–20.7%, 6.8–13.8% and 12.2–15.6%, and 5.5–11.7% and 10.0–16.0%, respectively. Meanwhile, the N partial factor productivity (PFPN), N agronomy use efficiency (ANUE), N recovery efficiency (NRE) and N uptake efficiency (NEupk) under the N240 treatment for spring wheat and summer maize obtained high levels of 20.99 and 47.01 kg−1, 9.27 and 16.35 kg−1, 32.53% and 32.44%, and 0.85 and 0.72 kg−1, respectively. Correlation analysis showed that the N application rate, TN and NEupk played significantly positive roles on GY, spring wheat spilke grain number, summer maize ear grain number and 1000–grain weight, DM LAImax and SPADmax, while NUEbms, NUEg, PFPN and ANUE always played negative effects. These results demonstrate that spring wheat, summer maize and annual cereal obtained the highest GY being 4654–5317, 11,727–12,003 and 16,349–16,658 kg ha−1 with the optimal N application rate 231–307, 222–337 and 463–571 kg ha−1, respectively, which provide N application guidance to farmer for spring wheat–summer maize crop systems to achieve annual mechanical harvesting in the thermal–resource–limited region of the North China Plain

Hypothermia activates adipose tissue to promote malignant lung cancer progression.

Microenvironment has been increasingly recognized as a critical regulator of cancer progression. In this study, we identified early changes in the microenvironment that contribute to malignant progression. Exposure of human bronchial epithelial cells (BEAS-2B) to methylnitrosourea (MNU) caused a reduction in cell toxicity and an increase in clonogenic capacity when the temperature was lowered from 37°C to 28°C. Hypothermia-incubated adipocyte media promoted proliferation in A549 cells. Although a hypothermic environment could increase urethane-induced tumor counts and Lewis lung cancer (LLC) metastasis in lungs of three breeds of mice, an increase in tumor size could be discerned only in obese mice housed in hypothermia. Similarly, coinjections using differentiated adipocytes and A549 cells promoted tumor development in athymic nude mice when adipocytes were cultured at 28°C. Conversely, fat removal suppressed tumor growth in obese C57BL/6 mice inoculated with LLC cells. Further studies show hypothermia promotes a MNU-induced epithelial-mesenchymal transition (EMT) and protects the tumor cell against immune control by TGF-β1 upregulation. We also found that activated adipocytes trigger tumor cell proliferation by increasing either TNF-α or VEGF levels. These results suggest that hypothermia activates adipocytes to stimulate tumor boost and play critical determinant roles in malignant progression

The hypothermia-activated adipocytes promoted lung cancer progression by TGF-β1 and TNF-α.

<p>A. TGF-β1 neutralization relative to MNU alone down-regulated epithelial marker E-cadherin and upregulated mesenchymal markers, such vimentin and fibronectin, and adding TGF-β1 to cells had opposite action in MNU-treated BEAS-2B cells (n = 5). B. TGF-β1 neutralization relative to control promoted CD8+ T cell-mediated cytotoxicity at 37°C and adding TGF-β1 to cells suppressed CD8+ cell-mediated cytotoxicity in A549 cells (n = 5). C. Xenografts of coinjection using A549 cells and 28°C-cultured adipocytes grew rapidly relative to A549 single injection (n = 10). D. A coinjection using either TNF-α or VEGF and A549 cells promoted xenograft development, whereas pre-cultured adipocytes by a TNF-α or VEGF blocking antibody prevented xenograft development relative to A549 single injection (n = 10). Data were expressed as mean ± SD. One asterisk (<b>*</b>)<0.001.</p