SARS coronavirus 7a protein blocks cell cycle progression at G0/G1 phase via the cyclin D3/pRb pathway

AbstractThe genome of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) contains four structural genes that are homologous to genes found in other coronaviruses, and also contains six subgroup-specific open reading frames (ORFs). Expression of one of these subgroup-specific genes, ORF7a, resulted in apoptosis via a caspase-dependent pathway. Here, we observed that transient expression of ORF7a protein fused with myc or GFP tags at its N or C terminus inhibited cell growth and prevented BrdU incorporation in different cultural cells, suggesting that ORF7a expression may regulate cell cycle progression. Analysis by flow cytometry demonstrated that ORF7a expression was associated with blockage of cell cycle progression at G0/G1 phase in HEK 293 cells after 24 to 60 h post-transfection. Similar results were observed in COS-7 and Vero cells. Mutation analysis of ORF7a revealed that the domain spanning aa 44–82 of 7a protein was essential for its cytoplasmic localization and for induction of the cell cycle arrest. After analyzing the cellular proteins involving in regulation of cell cycle progression, we demonstrated that ORF7a expression was correlated with a significant reduction of cyclin D3 level of mRNA transcription and expression, and phosphorylation of retinoblastoma (Rb) protein at ser795 and ser809/811, not with the expression of cyclin D1, D2, cdk4 and cdk6 in HEK 293 cells. These results suggest that the insufficient expression of cyclin D3 may cause a decreased activity of cyclin D/cdk4/6, resulting in the inhibition of Rb phosphorylation. Accumulation of hypo- or non-phosphorylated pRb thus prevents cell cycle progression at G0/G1 phase

Enhanced cisplatin chemotherapy sensitivity by self-assembled nanoparticles with Olaparib

Cisplatin (CDDP) is widely used as one kind of chemotherapy drugs in cancer treatment. It functions by interacting with DNA, leading to the DNA damage and subsequent cellular apoptosis. However, the presence of intracellular PARP1 diminishes the anticancer efficacy of CDDP by repairing DNA strands. Olaparib (OLA), a PARP inhibitor, enhances the accumulation of DNA damage by inhibiting its repair. Therefore, the combination of these two drugs enhances the sensitivity of CDDP chemotherapy, leading to improved therapeutic outcomes. Nevertheless, both drugs suffer from poor water solubility and limited tumor targeting capabilities. To address this challenge, we proposed the self-assembly of two drugs, CDDP and OLA, through hydrogen bonding to form stable and uniform nanoparticles. Self-assembled nanoparticles efficiently target tumor cells and selectively release CDDP and OLA within the acidic tumor microenvironment, capitalizing on their respective mechanisms of action for improved anticancer therapy. In vitro studies demonstrated that the CDDP-OLA NPs are significantly more effective than CDDP/OLA mixture and CDDP at penetrating cancer cells and suppressing their growth. In vivo studies revealed that the nanoparticles specifically accumulated at the tumor site and enhanced the therapeutic efficacy without obvious adverse effects. This approach holds great potential for enhancing the drugs’ water solubility, tumor targeting, bioavailability, and synergistic anticancer effects while minimizing its toxic side effects

Influence of loneliness burden on cardio-cerebral vascular disease among the Chinese older adult: a national cohort study

BackgroundAdverse psychosocial factors play an important role in cardio-cerebral vascular disease (CCVD). The aim of this study was to evaluate the impact of the cumulative burden of loneliness on the risk of CCVD in the Chinese older adult.MethodsA total of 6,181 Chinese older adult over the age of 62 in the monitoring survey of the fourth Sample Survey of the Aged Population in Urban and Rural China (SSAPUR) were included in this study. The loneliness cumulative burden (scored by cumulative degree) was weighted by the loneliness score for two consecutive years (2017–2018) and divided into low- and high-burden groups. The outcome was defined as the incidence of CCVD 1 year later (2018–2019). A multivariate logistic regression model was used to examine the relationship between the cumulative burden of loneliness and the new onset of CCVD.ResultsAmong participants, 18.9% had a higher cumulative burden of loneliness, and 11.5% had a CCVD incidence within 1 year. After multivariate adjustment, the risk of developing CCVD in the high-burden group was approximately 37% higher than that in the low-burden group (OR 1.373, 95%CI 1.096–1.721; p = 0.006). Similar results were obtained when calculating the burden based on cumulative time. Longitudinal change in loneliness was not significantly associated with an increased risk of CCVD. A higher cumulative burden of loneliness may predict a higher risk of developing CCVD in older adult individuals aged 62–72 years or in those with diabetes.ConclusionThe cumulative burden of loneliness can be used to assess the risk of new-onset CCVD in the older adult in the short term

Prevalence and pattern of multimorbidity in China: a cross-sectional study of 224,142 adults over 60 years old

AimTo examine the prevalence and potential risk factors of multimorbidity among older adult in China. In addition, we investigated the pattern of multimorbidity.MethodsThis study is based on data from the fourth Sample Survey of the Aged Population in Urban and Rural China (SSAPUR) in 2015, a comprehensive survey of individuals aged 60 years or older in China. We calculated baseline data and prevalence rates for comorbidities, stratified by household registration, age, sex, education, exercise, and health insurance. Univariate and multivariate logistic regression analyses were conducted to identify potential risk factors for comorbidities. Furthermore, we determined the prevalence rates for the three most frequent disease combinations.ResultsA total of 215,040 participants were included in our analysis. The prevalence of multimorbidity was 50.5% among the older adult in China. The prevalence rate was slightly higher in rural areas than in urban areas, with rates of 51.5 and 49.6%, respectively (p < 0.001). Moreover, the prevalence rate was higher in females than in males, with rates of 55.2 and 45.3%, respectively (p < 0.001). Multivariate logistic regression analysis revealed that individuals aged 70–79 years (OR:1.40, 95% CI: 1.38–1.43, p < 0.001) and over 80 years (OR:1.41, 95% CI: 1.38–1.45, p < 0.001) had a higher prevalence of multimorbidity than those aged 60–69 years. The most prevalent pair of comorbidities was hypertension and osteoarthropathy, with 19.6% of the participants having these two conditions, accounting for 5.4% of the total participants.ConclusionOur findings indicate a high prevalence of multimorbidity among the older adult in China. Increased expenditure on preventive health care, popularization of general medicine and popular medical education may be adopted by the Government to cope with the high prevalence of multimorbidity

Proteomic analysis of fertilized egg white during early incubation

AbstractProteomic analysis of egg white proteins was performed to elucidate their metabolic fates during first days of embryo development using 2-DE coupled with a LC–MS/MS. A total of 91 protein spots were analyzed, representing 37 proteins belonging to ‘Gallus gallus’, of 19 proteins were detected in egg whites for the first time, such as lipoproteins, vitellogenin and zona pellucida C protein. All ovomucoid spots with one exception were significantly (P<0.05) increased. Marker protein and one flavoprotein spot were significantly increased while hemopexin, serum albumin precursor, Ex-FABP precursor and Galline Ex-FABP were significantly decreased

Measuring the Impact of the Multiple Cropping Index of Cultivated Land during Continuous and Rapid Rise of Urbanization in China: A Study from 2000 to 2015

With the continuous and rapid rise of urbanization in China, land use transition research has been carried out extensively. Multiple cropping is the content of land use recessive morphology research, and it is also a common agricultural system in China. Accordingly, further research on multiple cropping index (MCI) can enrich the land use transition research and help to evaluate China’s food security. In order to examine the spatiotemporal changes and factors influencing the MCI of cultivated land in China, we collected MODIS remote sensing image data and land use classification data and conducted a remote sensing inversion on China’s MCI from 2000, 2005, 2010, and 2015. The spatial distributions and evolution processes of the MCI were explored through spatial mapping, statistical analysis, and processing with the Geographic Information System; moreover, the influencing factors of MCI were explored quantitatively with principal component regression. The results were as follows: (1) at the provincial scale, the average MCI across Guangdong, Guangxi, Hainan, Henan, Anhui, and Jiangsu was high; meanwhile, the average MCI across Heilongjiang, Inner Mongolia, Ningxia, and Qinghai was low. Between 2000 and 2015, the number of provinces with low MCI increased gradually, and the average MCI decreased greatly in the southern provinces. (2) At the county scale, the Taihang Mountains, Qinling Mountains, and Hengduan Mountains formed the boundary of China’s single cropping and multiple cropping indices. Dynamic changes in China’s MCI were obvious, and the number of counties with MCI change values lower than 0 increased gradually. Last, (3) natural conditions, nonagricultural process, cultivated land quality, and agricultural intensification demonstrated different degrees of impact on the MCI; in particular, the influence of nonagricultural industries, pesticides, and agricultural plastic film on the MCI proved especially important. Future research should strengthen the existing work on related transformations in farmers’ livelihoods, especially in terms of the return of rural labor force, the body of agricultural production, agricultural ecological issues, and the balance between increased crop production and reduced environmental pollution. In addition, agricultural policy design should pay more attention to cultivated land quality, the farmer who cultivates the land, and the multiple cropping potential of cultivated land

Purification and characterization of antioxidant peptides from cooked eggs using a dynamic in vitro gastrointestinal model in vascular smooth muscle A7r5 cells

Antioxidant peptides derived from food sources are considered as safer alternatives to commercially available antioxidant drugs. As one of the most abundant protein sources, hen’s egg proteins were extensively used to produce antioxidant peptides by enzymatic hydrolysis. Our previous work indicated that gastrointestinal digestion of cooked eggs significantly increased the antioxidant activity due to hydrolysis of egg proteins. To characterize the responsible antioxidant peptides, cooked eggs were digested in a simulated in vitro model of human gastro-intestinal digestion. Prepared digests were fractionated with FPLC (Fast Protein Liquid Chromatography) and RP-HPLC (Reverse-Phase High-Performance Liquid Chromatography) and the antioxidant activity was determined in A7r5 cells (vascular smooth muscle cell line). Further identification of peptides from peptide fractions with the highest antioxidant activity was carried out using LC-MS/MS. Four peptides derived from ovalbumin, DSTRTQ (48–53), DKLPG (61–65), DVYSF (96–100), and ESKPV (205–209), were identified; of which DKLPG did not show antioxidant activity in cells. Enzyme cleave analysis suggested that these four peptides were likely released from ovalbumin only by pepsin non-specific cleaves. It is postulated that egg consumption may exert protection against oxidative stress on human health due to release of antioxidant peptides during digestion

Multiscale Inversion of Leaf Area Index in Citrus Tree by Merging UAV LiDAR with Multispectral Remote Sensing Data

The LAI (leaf area index) is an important parameter describing the canopy structure of citrus trees and characterizing plant photosynthesis, as well as providing an important basis for selecting parameters for orchard plant protection operations. By fusing LiDAR data with multispectral data, it can make up for the lack of rich spatial features of multispectral data, thus obtaining higher LAI inversion accuracy. This study proposed a multiscale LAI inversion method for citrus orchard based on the fusion of point cloud data and multispectral data. By comparing various machine learning algorithms, the mapping relationship between the characteristic parameters in multispectral data and point cloud data and citrus LAI was established, and we established the inversion model based on this, by removing redundant features through redundancy analysis. The experiment results showed that the BP neural network performs the best at both the community scale and the individual scale. After removing redundant features, the R2, RMSE, and MAE of the BP neural network at the community scale and individual scale were 0.896, 0.112, 0.086, and 0.794, 0.408, 0.328, respectively. By adding the three-dimensional gap fraction feature to the two-dimensional vegetation index features, the R2 at community scale and individual scale increased by 4.43% and 7.29%, respectively. The conclusion of this study suggests that the fusion of point cloud and multispectral data exhibits superior accuracy in multiscale citrus LAI inversion compared to relying solely on a single data source. This study proposes a fast and efficient multiscale LAI inversion method for citrus, which provides a new idea for the orchard precise management and the precision of plant protection operation