MiR-494-3p mediates oxaliplatin resistance of colorectal cancer cells via PTEN/AKT pathway

Purpose: To unravel the influence of miR-494-3p on the insensitivity of colorectal cancer (CRC) cells to oxaliplatin.Methods: The mRNA level of miR-494-3p in oxaliplatin-resistant HT-29 cells was evaluated with reverse transcript-polymerase chain reaction (RT-PCR). The cells were treated with miR-494-3p suppressor or mimic, and then apoptotic changes were determined flow cytometrically. Resistancerelated gene expressions were measured using RT-PCR and western blotting. In addition, in vivo mouse experiments were conducted.Results: MiR-494-3p expression in oxaliplatin-resistant HT-29 cells was much higher than that in parental HT-29 cells, accompanied by increased levels of MRP, P-gp, and AKT phosphorylation (p-AKT), and decreased phosphatase and tensin homolog (PTEN) (p < 0.001). The miR-494-3p mimic suppressed oxaliplatin-induced parental HT-29 cell apoptosis, while miR-494-3p inhibitor promoted oxaliplatin-resistant HT-29 cell apoptosis and decreased the levels of p-AKT, MRP and P-gp, while upregulating PTEN (p < 0.001). Furthermore, AKT inhibitor had similar effects as miR-494-3p inhibitor (p < 0.001). Experiments using nude mice demonstrated that inhibition of miR-494-3p accentuated the sensitivity of oxaliplatin-resistant HT-29 cells to oxaliplatin (p < 0.05).Conclusion: Suppression of miR-494-3p attenuates oxaliplatin insensitivity to CRC cells via a mechanism which may involve PTEN/AKT pathway. Therefore, miR-494-3p may be an effective target for overcoming drug resistance of CRC

Mining Emotional Features of Movies

ABSTRACT In this paper, we present the algorithm designed for mining emotional features of movies. The algorithm dubbed Arousal-Valence Discriminant Preserving Embedding (AV-DPE) is proposed to extract the intrinsic features embedded in movies that are essentially differentiating in both arousal and valence directions. After dimensionality reduction, we use the neural network and support vector regressor to make the final prediction. Experimental results show that the extracted features can capture most of the discriminant information in movie emotions

Evaluation of Cardiac Structure and Function in Patients with Wilson Disease Based on RT-3DE: a Clinical Study

Background Wilson disease (WD) is a rare autosomal recessive disease that causes impaired copper excretion, mainly manifestedashepatic and/or neuropsychiatric symptoms, but diversifies with the varying affected organs and severity of the disease. The accumulation of copper in various organs and systems throughout the bodyleads to other (usually milder) clinical symptoms such as Kayser-fleischer ring (K-F), hemolytic disease, impaired renal function, abnormal bone metabolism, myocarditis, arrhythmias, other organ and systemic damage. It has been recently found that WD may result in varying degrees of cardiac damage and even fatal cardiac disorder inextensive studies. Clinical examination of the cardiovascular system has not been included in the routine testing of WD patients. Therefore, early attention and intervention of subclinical cardiac disease in WD patients are of great significance for the treatment and prognosis. Objective To observe the dynamic changes in cardiac structure and function in WD patients based on real-time three-dimensional transesophageal echocardiography (RT-3DE), electrocardiogram (ECG) and serological indicators such as myocardial injury markers, so as to provide objective imaging and serological basis for the assessment of early cardiac involvement in WD and facilitating timely intervention in WD patients with early subclinical cardiac damage. Methods From October 2021 to October 2022, 60 patients with WD admitted to the neurological department of the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine were selected as the WD group, and 60 healthy physical examiners were selected as the control group during the same time. The included WD patients were divided into the neurologic-type (mainly manifested as neuropsychiatric symptoms) and hepatic-type (mainly manifested ashepatic symptoms) groups according the mainsymptoms. ECG, RT-3DE-related parameters and serum myocardial injury markerssuch ashomocysteine (Hcy), cystatin C (CysC), cardiac troponin I (cTnI), amino-terminal B-type natriuretic peptide precursor (NT-proBNP), and total serum bilirubin (TBIL) of the both groups were recorded. Results There were significant differences in the proportion of abnormal ECG results between the two groups, with 37 abnormal cases in the WD group and 14 abnormal cases in the control group (P<0.001) ; compared with the control group, HR, QRS duration, QT interval were increased and P-R interval were decreased in the WD group (P<0.01). There were significant differences in the proportion of abnormal RT-3DE results between the two groups, with 23 abnormal cases in the WD group and 10 abnormal cases in the control group (P<0.001) ; compared with the control group, LAD, E/E', EDV, ESV, PAP were increased and E', EF, SV were decreased in the WD group (P<0.01). Compared with the control group, Hcy, TBIL, CysC, cTnI were increased in the WD group. Compared with the hepatic-type group, QRS duration, QT interval and QTc interval were increased (P<0.05), LAD, IVST, LVD, ESV, EDV were increased, SV was decreased (P<0.05), Hcy, CysC, cTnI were increased (P<0.01) in the neurologic-type group. Conclusion No features of structural heart disease were found in WD patients, however, WD patients had a higher risk of developing subclinical cardiac damage than healthy controls. In particular, neurologic-type WD patients had a higher risk of subclinical cardiac dysfunction, ventricular remodeling, and myocardial fibrosis than hepatic-type WD patients. RT-3DE technique has high value in assessing cardiac function in WD patients

Enhanced Gene Transfection Efficacy and Safety Through Granular Hydrogel Mediated Gene Delivery Process

Although gene therapy has made great achievements in both laboratory research and clinical translation, there are still challenges such as limited control of drug pharmacokinetics, acute toxicity, poor tissue retention, insufficient efficacy, and inconsistent clinical translation. Herein, a gene therapy gel is formulated by directly redispersing polyplex nanoparticles into granular hydrogels without any gelation pre-treatment, which provides great convenience for storage, dosing and administration. In vitro studies have shown that use of granular hydrogels can regulate the gene drug release, reduce dose dependent toxicity and help improve transfection efficacy. Moreover, the developed gene therapy gel is easy to operate and can be directly used in vitro to evaluate its synergistic efficacy with various gene delivery systems. As such, it represents a major advance over many conventional excipient-based formulations, and new regulatory strategies for gene therapy may be inspired by it

Hippo信号通路通过调控Skp2活性从而抑制细胞多倍体产生及肝癌发生

文章简介在这项研究中,课题组揭示了Hippo信号通路在限制肝脏细胞的染色体由两倍体向多倍/非整倍体转变过程中起关键作用,该机制异常将导致基因组不稳定继而诱发肝癌的发生发展。课题组通过对Hippo信号通路重要成员(WW45,Mst1/2,Lats1/2)肝脏特异性敲除和过表达国家自然科学基金委;;国家重点基础研究发展计划(973)项目;;青年千人计划;;中央高校基本科研基金的资

Exploring the Factors Driving Seasonal Farmland Abandonment: A Case Study at the Regional Level in Hunan Province, Central China

Farmland abandonment, including perennial and seasonal abandonment, is an important process of land use change that matters most to food security. Although there is a great deal of studies on farmland abandonment, seasonal abandonment, which is as serious as perennial abandonment, has attracted little academic attention. This paper takes Hunan Province in central China as its study area and uses a spatial regression model to examine the driving factors of seasonal farmland abandonment at the county level. Our results show that farmland abandonment has striking spatial relativity, and there are two clustering zones with a high index of farmland abandonment (IFA) in the Dongting plain and the basin in south-central Hunan, while a clustering zone of low IFA can be found in the mountains of southwest Hunan. Farmland abandonment at the regional level is negatively affected by the land productive potentialities, proportion of mechanized planting, ratio of effective irrigation, and distance to provincial capital, while it is positively associated with the variables mountainous terrain, per capita farmland area, and labor shortage. Additionally, farmland abandonment is also affected by adjacent areas through its spatial dependence. In short, seasonal farmland abandonment is also driven integratedly by the socioeconomic and environmental dimensions and spatial interaction of farm abandonment

RESEARCH ON ISOTHERMAL FORGING OF ALUMINUM ALLOYAUTOMOBILE DIFFERENTIAL CASE

In order to solve the problem of complex housing shape and difficult forging forming of new lightweight aluminum alloy automobile differential housing based on the present production status of conventional casting molding and cast steel materials, a 7075 aluminum alloy automobile differential housing are used as the research objects, the finite simulation software Deform is used to simulate the isothermal forging type, and the experimental method is used to verify the accuracy of the simulation analysis. The results show that in the isothermal forging process of the differential housing, the blank is gradually formed into a differential housing with the shape of the fixed lower die under the motion action of die forging and pressing; the maximum equivalent stress mainly occurs in the complex shape and the transition point of sudden change of the differential housing; the tensile strength and the yield strength are different at different positions, but the variation range is small; with the increase of the isothermal forging temperature, the tensile strength and yield strength of the forged differential housing piece show the trend of first increasing and then decreasing, and the best isothermal forging is 425℃. The research provides an important reference for the optimization design and life improvement of the isothermal forging die of the differential housing and the production and application of the lightweight aluminum alloy differential housing

Exploring the Factors Driving Seasonal Farmland Abandonment: A Case Study at the Regional Level in Hunan Province, Central China

Farmland abandonment, including perennial and seasonal abandonment, is an important process of land use change that matters most to food security. Although there is a great deal of studies on farmland abandonment, seasonal abandonment, which is as serious as perennial abandonment, has attracted little academic attention. This paper takes Hunan Province in central China as its study area and uses a spatial regression model to examine the driving factors of seasonal farmland abandonment at the county level. Our results show that farmland abandonment has striking spatial relativity, and there are two clustering zones with a high index of farmland abandonment (IFA) in the Dongting plain and the basin in south-central Hunan, while a clustering zone of low IFA can be found in the mountains of southwest Hunan. Farmland abandonment at the regional level is negatively affected by the land productive potentialities, proportion of mechanized planting, ratio of effective irrigation, and distance to provincial capital, while it is positively associated with the variables mountainous terrain, per capita farmland area, and labor shortage. Additionally, farmland abandonment is also affected by adjacent areas through its spatial dependence. In short, seasonal farmland abandonment is also driven integratedly by the socioeconomic and environmental dimensions and spatial interaction of farm abandonment

Assessing the Spatiotemporal Dynamics of Vegetation Coverage in Urban Built-Up Areas

As the main carbon sink in the carbon cycle process, vegetation is an important support for achieving “carbon peaking” and “carbon neutrality. How does the vegetation coverage of urban built-up areas change in the process of urbanization in China? Taking advantage of Landsat remote sensing data, we extract urban built-up areas, calculate the Normalized Difference Vegetation Index (NDVI), estimate fractional vegetation cover (FVC), and analyze the temporal and spatial dynamics of vegetation coverage in built-up areas of provincial capitals from the national and individual city levels in China. Major conclusions are as follows: (1) The FVC in the urban built-up areas has increased by 7.97%, and the urban green space has gradually changed from the “green core” distribution model to the “green vein” distribution mode. (2) The disparities in FVC of built-up areas of provincial capitals are notable, presumably due to a variety of factors that include the natural geographic environment, economic development level, built-up area expansion, land type conversion, afforestation of greening policy, etc. (3) Not just simply raise or lower, the FVC curves in the built-up areas of provincial capital cities present oscillating patterns with gradually weakening amplitude. Our study is expected to provide scientific references of an important theoretical basis for urban ecological construction and practical support for promoting the harmonious development of urban residents and urban environments in China

The Pattern and Local Push Factors of Rural Depopulation in Less-Developed Areas: A Case Study in the Mountains of North Hebei Province, China

Rural depopulation is the most significant geographical phenomenon in rural areas during the process of urbanization. Although many studies have investigated the driving force of rural depopulation based on rural-urban migration at the macro level, the local factors, and their impact on rural depopulation from the rural areas have been not fully revealed. This paper selected the northern mountains of China’s Hebei province as a study area to explore the pattern and local push factors of rural depopulation at the rural-township levels based on GeoDetector. The main findings are summarized as follows. (1) Rural depopulation varies substantially, demonstrates spatial correlation, and is distributed in clusters. From a dynamic perspective, compare that in years 2000–2010, the population growth areas during 2010–2017 have been significantly expanded, while the sharp depopulation areas and severe depopulation areas experienced shrinkage in our study area. (2) The pattern of rural depopulation is in accordance with terrain. Rural depopulation tends to be stronger in plateaus and mountains, while relatively milder in intermontane basins, hills, and piedmont plains. (3) The agricultural suitability of natural environmental and rural economic opportunities together with climate changes were the most important driving forces of rural depopulation at local levels. Location, sparse population, and inadequate public services also contributed to rural depopulation. However, the dominant driving factors are different in the different periods. Rural depopulation was mainly driven by arable land per capita and natural environmental variables in the years 2000–2010, while the population density, location, and off-farm economic opportunities played a decisive role in the years 2010–2017. (4) Rural depopulation is a complex, multi-dimensional process driven by a combination of multiple factors including different environmental factors, economic opportunities, and location. This paper reveals the push factors of rural depopulation in underdeveloped mountainous areas by a quantitative empirical approach, inspiring increased attention to the impacts of local factors and spatial correlations on rural depopulation, and has many implications for the policy design of China’s rural revitalization