RESUMO
Bladder cancer is characterized by aberrant activation of the phosphatidylinositol-3-OH kinase (PI3K) signaling, underscoring the significance of directing therapeutic efforts toward the PI3K pathway as a promising strategy. In this study, we discovered that PI3K serves as a potent therapeutic target for bladder cancer through a high-throughput screening of inhibitory molecules. The PI3K inhibitor demonstrated a robust anti-tumor efficacy, validated both in vitro and in vivo settings. Nevertheless, the feedback activation of JAK1-STAT3 signaling reinstated cell and organoid survival, leading to resistance against the PI3K inhibitor. Mechanistically, the PI3K inhibitor suppresses PTPN11 expression, a negative regulator of the JAK-STAT pathway, thereby activating STAT3. Conversely, restoration of PTPN11 enhances the sensitivity of cancer cells to the PI3K inhibitor. Simultaneous inhibition of both PI3K and STAT3 with small-molecule inhibitors resulted in sustained tumor regression in patient-derived bladder cancer xenografts. These findings advocate for a combinational therapeutic approach targeting both PI3K and STAT3 pathways to achieve enduring cancer eradication in vitro and in vivo, underscoring their promising therapeutic efficacy for treating bladder cancer.
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The convex reflective diffraction grating is an essential optical component in Offner systems, which has been widely used in imaging spectrometers. We propose a new design and optimization method for the convex blazed grating in the Offner imaging spectrometer. The method integrates the macro- and microdesign of the optical system, and it can be used to design and optimize the convex blazed grating with high diffraction efficiency. Traditional geometric optics theory and image quality evaluation methods are used to design the macro-optical structure parameters of the Offner system. And then the incident ray information, such as the incident angle and the polarization states are calculated by using the three-dimensional polarization ray-tracing method. To improve the diffraction efficiency, we combine rigorous coupled wave analysis and a particle swarm optimization algorithm to optimize the microstructure parameters of the convex-blazed grating. Further, a convex-blazed grating in a mid-wave infrared Offner imaging spectrometer is designed as an example to illustrate our design method in detail. The design results indicate that the Offner imaging spectrometer has good imaging quality, and the average diffraction efficiency of the -1st diffraction order of the convex-blazed grating in the spectral coverage 3-5 µm is 82.24%. Compared to the traditional design method, the lowest spectral diffraction efficiency is improved from 59.88% to 69.24%, the highest spectral diffraction efficiency is improved from 90.45% to 91.84%, and the standard deviation is reduced from 7.82 to 6.62.
RESUMO
Straw retention is an effective method to conserve soil water content and improve soil carbon stocks. However, how soil carbon dynamics respond to different straw retention practices remains unclear. In this study, we investigated soil respiration and soil carbon sequestration at depths of 0-100 cm. We conducted a two-year field experiment with three crop rotation treatments and three straw retention treatments in northwest China. The straw retention treatments included no straw retention (NS), retention of half the straw (HS), and retention of the total amount of straw (TS). The crop rotations treatments included winter wheat plus summer soybean (WS), winter wheat plus summer maize (WM), and winter wheat plus summer fallow (WF). Mean soil respiration rates under WS, WM, and WF treatments were 5.14, 6.53, and 5.49 µmol·m-2·s-1; and 5.67, 5.47, and 6.03 µmol·m-2·s-1 under TS, HS, and NS treatments. The mean soil water content were 15.50%, 15.57%, and 15.74% under WS, WM, and WF rotations, and 15.81%, 15.41%, and 15.50% under TS, HS, and NS treatments. The soil organic carbon (SOC) concentration was higher with increased straw retention, and lower at deeper soil depths. Mean SOC concentrations under different rotations and straw treatments of TS, HS, and NS, respectively were as follows: WS: 6.91, 6.63, 6.39 g/kg; WM: 6.90, 6.72, 6.57 g/kg; and WF: 6.49, 6.52, 6.37 g/kg. Soil temperature was the main determinant of soil respiration rates. We conclude that WS rotation resulted in lower soil respiration, WM rotation resulted in a higher soil carbon sequestration potential, and WF rotation resulted in higher soil water content. However, continued, long-term monitoring is needed to confirm the effect of rotations and straw retention on soil respiration and carbon sequestration in dryland cropping systems in northern China.
Assuntos
Agricultura , Produtos Agrícolas , Agricultura Orgânica , Solo , Agricultura/métodos , Carbono/análise , Sequestro de Carbono , Meio Ambiente , Solo/química , Temperatura , ÁguaRESUMO
Understanding the dynamics of ring polymers is a particularly challenging yet interesting problem in soft materials. Despite recent progress, a complete understanding of the nonequilibrium behavior of ring polymers has not yet been achieved. In this work, we directly observe the flow dynamics of DNA-based rings in semidilute linear polymer solutions using single molecule techniques. Our results reveal strikingly large conformational fluctuations of rings in extensional flow long after the initial transient stretching process has terminated, which is observed even at extremely low concentrations (0.025 c*) of linear polymers in the background solution. The magnitudes and characteristic timescales of ring conformational fluctuations are determined as functions of flow strength and polymer concentration. Our results suggest that ring conformational fluctuations arise due to transient threading of linear polymers through open ring chains stretching in flow.
RESUMO
The direct electrophilic α-cyanation of ß-keto esters and amides has been developed using a hypervalent iodine benziodoxole-derived cyano reagent. The procedure is accomplished within 10 min and without the use of any catalyst in DMF, at room temperature. Thus, the highly functionalized quaternary carbon-centered nitriles were produced in high to excellent yields.