Reversion of pH-Induced Physiological Drug Resistance: A Novel Function of Copolymeric Nanoparticles

The extracellular pH of cancer cells is lower than the intracellular pH. Weakly basic anticancer drugs will be protonated extracellularly and display a decreased intracellular concentration. In this study, we show that copolymeric nanoparticles (NPs) are able to overcome this “pH-induced physiological drug resistance” (PIPDR) by delivering drugs to the cancer cells via endocytosis rather than passive diffussion.As a model nanoparticle, Tetradrine (Tet, Pka 7.80) was incorporated into mPEG-PCL. The effectiveness of free Tet and Tet-NPs were compared at different extracellular pHs (pH values 6.8 and 7.4, respectively) by MTT assay, morphological observation and apoptotic analysis in vitro and on a murine model by tumor volume measurement, PET-CT scanning and side effect evaluation in vivo.<0.05) when the extracellular pH decreased from 7.4 to 6.8. Meanwhile, the cytotoxicity of Tet-NPs was not significantly influenced by reduced pH. In vivo experiment also revealed that Tet-NPs reversed PIPDR more effectively than other existing methods and with much less side effects.The reversion of PIPDR is a new discovered mechanism of copolymeric NPs. This study emphasized the importance of cancer microenvironmental factors in anticancer drug resistance and revealed the superiority of nanoscale drug carrier from a different aspect

Effects of anthropogenic and natural environmental factors on the spatial distribution of trace elements in agricultural soils

The concentrations of trace elements in agricultural soils directly affect the ecological security and quality of agricultural products. A comprehensive study aimed at quantitatively analyze the effects of anthropogenic and natural environmental factors on the spatial distribution of heavy metals (HMs) and selenium (Se) in agricultural soils in a typical grain producing area of China. Factors considered in this study were parent rock, soil physicochemical properties, topography, precipitation, mine activity, and vegetation. Results showed that the median values of Zn, Cd, Cr, and Cu of 111 topsoil samples exceeded the background values of Guangxi province but were lower than the relevant national soil quality standards, and 85% of soil samples were classified as having rich Se levels (0.40 −3.0 mg kg−1). The potential ecological risk index of soil heavy metals as a whole was low, with Cd in 9% of the samples posing moderate ecological risk. The concentrations of heavy metals and Se were relatively high in soils from shale rock. Soil properties, mainly Fe2O3 and Mn played a dominant role on soil HMs and Se concentrations. Based on GeoDetector, we found that the interaction effects of two factors on the spatial differentiation of soil HMs and Se were greater than their sum effect. Among the factors, Mn enhanced the explanatory power of the model the most when interacting with other factors for soil Zn; the greatest interactive effect was between distance from mining area and Mn for Cd (q = 0.70); Fe2O3 significantly promoted the spatial differentiation of soil Cr, Cu and Se when interacting with other factors (q > 0.50). These findings contribute to a better understanding of the factors that drive the distribution of HMs and Se in agricultural soils

Development and validation of a nomogram for predicting survival in patients with malignant myofibroblastic tumor

Abstract Background Malignant myofibroblastic tumors are a rare group of soft tissue sarcomas, for which a prognosis prediction model is lacking. Based on the Surveillance, Epidemiology, and End Results (SEER) database and cases from Nanjing Drum Tower Hospital, the current study constructed and validated a nomogram to assess overall survival of patients with malignant myofibroblastic tumors. Methods Data of patients with myofibroblastic tumors diagnosed between 2000 and 2018 were extracted from the SEER database. Similarly, data of patients with myofibroblastic tumor in Nanjing Drum Tower Hospital between May 2016 and March 2022 were collected. Then, we conducted univariate and multivariate Cox analyses to identify independent prognostic parameters to develop the nomogram. The model was evaluated by concordance index (C‐index), calibration curve, the area under the curve (AUC), decision curve analysis (DCA), Kaplan–Meier analysis, and subgroup analyses. Results Seven variables were selected to construct the nomogram. The results of the C‐index (0.783), calibration curve, the AUCs, and subgroup analyses demonstrated the accurate predictive capacity and excellent discriminative ability of the nomogram. The DCA of the model indicated its better clinical net benefit than that of the traditional system. Conclusion Evaluation of the predictive performance of the nomogram revealed the superior sensitivity and specificity of the model and the higher prediction accuracy of the outcomes compared with those of the traditional system. The established nomogram may assist patients in consultation and help physicians in clinical decision‐making

Improving Soil Enzyme Activities and Related Quality Properties of Reclaimed Soil by Applying Weathered Coal in Opencast-Mining Areas of the Chinese Loess Plateau

There are many problems for the reclaimed soil in opencast-mining areas of the Loess Plateau of China such as poor soil structure and extreme poverty in soil nutrients and so on. For the sake of finding a better way to improve soil quality, the current study was to apply the weathered coal for repairing soil media and investigate the physicochemical properties of the reclaimed soil and the changes in enzyme activities after planting Robinia pseucdoacacia. The results showed that the application of the weathered coal significantly improved the quality of soil aggregates, increased the content of water stable aggregates, and the organic matter, humus, and the cation exchange capacity of topsoil were significantly improved, but it did not have a significant effect on soil pH. Planting R. pseucdoacacia significantly enhanced the activities of soil catalase, urease, and invertase, but the application of the weathered coal inhibited the activity of catalase. Although the application of appropriate weathered coal was able to significantly increase urease activity, the activities of catalase, urease, or invertase had a close link with the soil profile levels and time. This study suggests that applying weathered coals could improve the physicochemical properties and soil enzyme activities of the reclaimed soil in opencast-mining areas of the Loess Plateau of China and the optimum applied amount of the weathered coal for reclaimed soil remediation is about 27?000?kg?hm-2.There are many problems for the reclaimed soil in opencast-mining areas of the Loess Plateau of China such as poor soil structure and extreme poverty in soil nutrients and so on. For the sake of finding a better way to improve soil quality, the current study was to apply the weathered coal for repairing soil media and investigate the physicochemical properties of the reclaimed soil and the changes in enzyme activities after planting Robinia pseucdoacacia. The results showed that the application of the weathered coal significantly improved the quality of soil aggregates, increased the content of water stable aggregates, and the organic matter, humus, and the cation exchange capacity of topsoil were significantly improved, but it did not have a significant effect on soil pH. Planting R. pseucdoacacia significantly enhanced the activities of soil catalase, urease, and invertase, but the application of the weathered coal inhibited the activity of catalase. Although the application of appropriate weathered coal was able to significantly increase urease activity, the activities of catalase, urease, or invertase had a close link with the soil profile levels and time. This study suggests that applying weathered coals could improve the physicochemical properties and soil enzyme activities of the reclaimed soil in opencast-mining areas of the Loess Plateau of China and the optimum applied amount of the weathered coal for reclaimed soil remediation is about 27?000?kg?hm-2

Rapid Identification of Main Vegetation Types in the Lingkong Mountain Nature Reserve Based on Multi-Temporal Modified Vegetation Indices

Nature reserves are among the most bio-diverse regions worldwide, and rapid and accurate identification is a requisite for their management. Based on the multi-temporal Sentinel-2 dataset, this study presents three multi-temporal modified vegetation indices (the multi-temporal modified normalized difference Quercus wutaishanica index (MTM-NDQI), the multi-temporal modified difference scrub grass index (MTM-DSI), and the multi-temporal modified ratio shaw index (MTM-RSI)) to improve the classification accuracy of the remote sensing of vegetation in the Lingkong Mountain Nature Reserve of China (LMNR). These three indices integrate the advantages of both the typical vegetation indices and the multi-temporal remote sensing data. By using the proposed indices with a uni-temporal modified vegetation index (the uni-temporal modified difference pine-oak mixed forest index (UTM-DMI)) and typical vegetation indices (e.g., the ratio vegetation index (RVI), the difference vegetation index (DVI), and the normalized difference vegetation index (NDVI)), an optimal feature set is obtained that includes the NDVI of December, the NDVI of April, and the UTM-DMI, MTM-NDQI, MTM-DSI, and MTM-RSI. The overall accuracy (OA) of the random forest classification (98.41%) and Kappa coefficient of the optimal feature set (0.98) were higher than those of the time series NDVI (OA = 96.03%, Kappa = 0.95), the time series RVI (OA = 95.56%, Kappa = 0.95), and the time series DVI (OA = 91.27%, Kappa = 0.90). The OAs of the rapid classification and the Kappa coefficient of the knowledge decision tree based on the optimal feature set were 95.56% and 0.95, respectively. Meanwhile, only three of the seven vegetation types were omitted or misclassified slightly. Overall, the proposed vegetation indices have advantages in identifying the vegetation types in protected areas

Application Progress of Aerogel / Inorganic Cementitious Composites in Building Thermal Insulation

In recent years, the problem of energy saving and consumption reduction in the construction industry has attracted more and more attention. The state has also put forward higher requirements on the energy saving, environmental protection and fire safety of building exterior wall insulation in terms of policies. Aerogel materials are considered to be the most promising thermal insulation materials in the future due to their excellent thermal insulation properties and fire resistance. In this paper, the preparation process and application of aerogel inorganic cementitious composites were investigated, mainly aerogel cement composites and aerogel gypsum composites. We analyzed the recent research results, and focused on the preparation optimization and application prospects of aerogel inorganic cementitious composites. In the preparation of aerogel inorganic cementitious composites, many researchers have proposed different preparation methods to optimize the interface between aerogel and inorganic cementitious materials in order to avoid the strength degradation caused by doping aerogel. At present, preparing aerogel into aerogel slurry for compounding is considered to be a relatively optimal incorporation method. It is found that aerogel inorganic cementitious composites have great prospects for thermal insulation applications in the construction field. However, due to the high cost of aerogel preparation and the poor interfacial bonding between aerogel and inorganic cementitious materials, the application of aerogel in building thermal insulation is limited. This paper has reference significance for studying the application of aerogel in the construction industry

Biocompatible Nanoparticles as a Platform for Enhancing Antitumor Efficacy of Cisplatin-Tetradrine Combination

Combination therapy has been a standard strategy in the clinical tumor treatment. We have demonstrated that combination of Tetradrine (Tet) and Cisplatin (CDDP) presented a marked synergistic anticancer activity, but inevitable side effects limit their therapeutic concentration. Considering the different physicochemical and pharmacokinetic properties of the two drugs, we loaded them into a nanovehicle together by the improved double emulsion method. The nanoparticles (NPs) were prepared from the mixture of poly(ethyleneglycol)-polycaprolactone (PEG-PCL) and polycarprolactone (HO-PCL), so CDDP and Tet can be located into the NPs simultaneously, resulting in low interfering effect and high stability. Images from fluorescence microscope revealed the cellular uptake of both hydrophilic and hydrophobic agents delivered by the NPs. In vitro studies on different tumor cell lines and tumor tissue revealed increased tumor inhibition and apoptosis rates. As to the in vivo studies, superior antitumor efficacy and reduced side effects were observed in the NPs group. Furthermore, (18)FDG-PET/CT imaging demonstrated that NPs reduced metabolic activities of tumors more prominently. Our results suggest that PEG-PCL block copolymeric NPs could be a promising carrier for combined chemotherapy with solid efficacy and minor side effects.Funding Agencies|Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81972192, 81972309]; Primary Research &amp; Development Plan of Jiangsu Province [BE2020619]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [2020-211]</p

Impedance Modeling and Stability Analysis for Cascade System of Three-Phase PWM Rectifier and LLC Resonant Converter

In this paper; the impedance model of PWM rectifier and LLC resonant converter are deduced, and the stability analysis of cascade system is studied. The principle of three-phase PWM rectifier is introduced; and the small signal model in d-q coordinate system is deduced. The expression of dc side output impedance model for PWM rectifier is derived. The LLC resonant converter is operated in a fixed-frequency state, and the LLC resonant converter is modeled as a small signal model. On this basis, the input impedance model expression of the LLC resonant converter is derived. According to the impedance stability criterion, it can seen that the amplitude of input impedance is greater than the amplitude of output impedance in a certain frequency domain. In addition, the Nyquist curve is not around the point (&#8722;1,0), which can judge that the cascade system is stable. In simulation software, a cascade system simulation is built and corresponding simulation curves are obtained, which verifies the stability of the cascade system