Liposomes are the first and mostly explored nanocarriers for cancer drug delivery, which have shown great promise in clinical applications, but their limited accumulation and penetration into the tumor interstitial space, significantly reduce the therapeutic efficacy. Here, a γ‐glutamyltranspeptidase (GGT)‐triggered charge‐switchable approach is reported that can trigger the fast endocytosis and transcytosis of the liposome in tumor microenvironments to overcome the harsh biological barriers in tumor tissues. The active transporting liposomal nanocarrier (GCSDL) is prepared by surface modification with a glutathione (GSH) moiety and encapsulated with doxorubicin (DOX). When the GCSDL contacts with tumor vascular endothelial cells, the overexpressed GGT enzyme on cytomembrane catalyzes the hydrolysis of GSH to generate cationic primary amines. The cationic GCSDL triggers fast caveolae‐mediated endocytosis and vesicle‐mediated transcytosis, resulting in sequential transcytosis to augment its tumor accumulation and penetration. Along with continual intercellular transportation, GCSDL can release DOX throughout the tumor to induce cancer cell apoptosis, resulting in complete eradication of hepatocellular carcinoma and cessation of pancreatic ductal adenocarcinoma's progression. This study develops an efficient strategy to realize high tumor accumulation and deep penetration for the liposomal drug delivery system via active transcytosis.
The low-carbon economic model is based on low energy consumption, low pollution, low emission; it is another major advancement of human society following agricultural civilization and industrial civilization. Low-carbon economy with its unique advantages and huge market has become a hot spot of world economic development. Now western region in China is facing two major tasks of the leapfrog development and sustainable development, as the less developed areas and the Wenchuan quake-hit, Guang Yuan has its representation and specificity. To achieve low-carbon reconstruction and sustainable development, how to choose a low-carbon path is very important for Guang Yuan. In this paper, it analyzed the advantage, weaknesses, opportunities and threats by SWOT method, and then proposed a feasible path for Guang Yuan's low-carbon development; it also hoped to provide a reference for the scientific development of underdeveloped areas.
Background. Acute ST-segment elevation myocardial infarction (STEMI) is a serious cardiovascular disease that poses a great threat to the life and health of patients. Therefore, early diagnosis is important for STEMI patient treatment and prognosis. The purpose of this study was to investigate the value of serum YKL-40 and TNF-α in the diagnosis of STEMI. Methods. From October 2020 to February 2022, 120 patients with STEMI were admitted to the Chest Pain Center of the Second People’s Hospital of Hefei, and 81 patients with negative coronary angiography were selected as the control group. Serum YKL-40 and TNF-α concentrations were measured by sandwich ELISA. Pearson correlation was used to analyze the correlation between serum YKL-40, TNF-α, and serum troponin I (cTnI) in STEMI patients; multivariate logistic regression analysis was used to screen independent risk factors for STEMI. Three diagnostic models were constructed: cTnI univariate model (model A), combined serum YKL-40 and TNF-α model other than cTnI (model B), and combined cTnI and serum YKL-40 and TNF-α model (model C). We assessed the clinical usefulness of the diagnostic model by comparing AUC with decision curve analysis (DCA). Results. Serum YKL-40 and TNF-α in the STEMI group were significantly higher than those in the control group (
P
<
0.001
). On Pearson correlation analysis, there was a significant positive correlation between serum YKL-40, TNF-α, and cTnI levels in STEMI patients. Multivariate logistic regression analysis showed that serum YKL-40 and TNF-α were independent risk factors for the development of STEMI. The results of ROC analysis showed that the area under the curve (AUC) of serum YKL-40 for predicting the occurrence of STEMI was 0.704. The AUC of serum TNF-α for predicting the occurrence of STEMI was 0.852. The AUC of cTnI as a traditional model, model A, for predicting the occurrence of STEMI was 0.875. Model B predicted STEMI with an AUC of 0.851. The addition of serum YKL-40 and serum TNF-α to the traditional diagnostic model composed of cTnI constituted a new diagnostic model; that is, the AUC of model C for predicting the occurrence of STEMI was 0.930. Model C had a better net benefit between a threshold probability of 70–95% for DCA. Conclusion. In this study, we demonstrate the utility of serum YKL-40 and TNF-α as diagnostic markers for STEMI and the clinical utility of diagnostic models by combining serum YKL-40 and TNF-α with cTnI.
Colorectal cancer (CRC) is one of the most common malignant tumors. Tumor-associated macrophages (TAMs) promote the progression of CRC, but the mechanism is not completely clear. The present study aimed to reveal the expression and function of FAM198B in TAMs, and the role of FAM198B in mediating macrophage polarization in CRC. The role of FAM198B in macrophage activity, cell cycle, and angiogenesis was evaluated by CCK-8 assay, flow cytometry, and vasculogenic mimicry assay. The effects of FAM198B on macrophage polarization were determined by flow cytometry. The function of FAM198B-mediated macrophage polarization on CRC progression was evaluated by transwell assays. Bioinformatic analyses and rescue assays were performed to identify biological functions and signaling pathways involved in FAM198B regulation of macrophage polarization. Increased FAM198B expression in TAMs is negatively associated with poor CRC prognosis. Functional assays showed that FAM198B promotes M2 macrophage polarization, which leads to CRC cell proliferation, migration, and invasion. Mechanistically, FAM198B regulates the M2 polarization of macrophages by targeting SMAD2, identifying the SMAD2 pathway as a mechanism by which FAM198B promotes CRC progression through regulating macrophage polarization. These findings provide a possible molecular mechanism for FAM198B in TAMs in CRC and suggest that FAM198B may be a novel therapeutic target in CRC.
Objective
Our aim is to establish a machine-learning model that will enable us to investigate the key factors influencing the prevalence of myopia in students.
Methods
We performed a cross-sectional study that included 16,653 students from grades 1–3 across 17 cities in Hubei Province. We used questionnaires to discern levels of participation in potential factors contributing to the development of myopia. The relative importance of potential contributors was ranked using machine-learning methods. The students’ visual acuity (VA) was measured and those with logMAR VA of > 0.0 underwent a autorefraction test to determine students’ refraction status.
Results
The prevalence of myopia in grades 1, 2, and 3 was 14.70%, 20.54% and 28.93%, respectively. Myopia rates among primary school students in provincial capital city (32.35%) were higher than those in other urban (23.03%) and rural (14.82%) areas. Children with non-myopic parents, only one myopic parent, or both parents having myopia exhibited myopic rates of 16.36%, 25.18%, and 41.37%, respectively. Myopia prevalence was higher in the students who continued to use their eyes at close range for a long time and lower in those engaged longer in outdoor activities. The machine-learning model determined that the top three contributing factors were the students’ age (0.36), followed by place of residence (0.34), starting age of education (0.21).
Conclusion
The overall prevalence of myopia was 21.52%. Children’s age and place of residence were the important influencing factors, but genetics and environmental were also played key roles in myopia development.
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