Biomedical and biological science
http://hdl.handle.net/10547/613703
2024-03-29T08:05:27ZInfluence of Environmental Factors and Genome Diversity on Cumulative COVID-19 Cases in the Highland Region of China: Comparative Correlational Study.
http://hdl.handle.net/10547/626209
Influence of Environmental Factors and Genome Diversity on Cumulative COVID-19 Cases in the Highland Region of China: Comparative Correlational Study.
Deji, Zhuoga; Tong, Yuantao; Huang, Honglian; Zhang, Zeyu; Fang, Meng; Crabbe, M. James C.; Zhang, Xiaoyan; Wang, Ying
Background: The novel coronavirus SARS-CoV-2 caused the global COVID-19 pandemic. Emerging reports support lower mortality and reduced case numbers in highland areas; however, comparative studies on the cumulative impact of environmental factors and viral genetic diversity on COVID-19 infection rates have not been performed to date. Objective: The aims of this study were to determine the difference in COVID-19 infection rates between high and low altitudes, and to explore whether the difference in the pandemic trend in the high-altitude region of China compared to that of the lowlands is influenced by environmental factors, population density, and biological mechanisms. Methods: We examined the correlation between population density and COVID-19 cases through linear regression. A zero-shot model was applied to identify possible factors correlated to COVID-19 infection. We further analyzed the correlation of meteorological and air quality factors with infection cases using the Spearman correlation coefficient. Mixed-effects multiple linear regression was applied to evaluate the associations between selected factors and COVID-19 cases adjusting for covariates. Lastly, the relationship between environmental factors and mutation frequency was evaluated using the same correlation techniques mentioned above. Results: Among the 24,826 confirmed COVID-19 cases reported from 40 cities in China from January 23, 2020, to July 7, 2022, 98.4% (n=24,430) were found in the lowlands. Population density was positively correlated with COVID-19 cases in all regions (ρ=0.641, P=.003). In high-altitude areas, the number of COVID-19 cases was negatively associated with temperature, sunlight hours, and UV index (P=.003, P=.001, and P=.009, respectively) and was positively associated with wind speed (ρ=0.388, P<.001), whereas no correlation was found between meteorological factors and COVID-19 cases in the lowlands. After controlling for covariates, the mixed-effects model also showed positive associations of fine particulate matter (PM2.5) and carbon monoxide (CO) with COVID-19 cases (P=.002 and P<.001, respectively). Sequence variant analysis showed lower genetic diversity among nucleotides for each SARS-CoV-2 genome (P<.001) and three open reading frames (P<.001) in high altitudes compared to 300 sequences analyzed from low altitudes. Moreover, the frequencies of 44 nonsynonymous mutations and 32 synonymous mutations were significantly different between the high- and low-altitude groups (P<.001, mutation frequency>0.1). Key nonsynonymous mutations showed positive correlations with altitude, wind speed, and air pressure and showed negative correlations with temperature, UV index, and sunlight hours. Conclusions: By comparison with the lowlands, the number of confirmed COVID-19 cases was substantially lower in high-altitude regions of China, and the population density, temperature, sunlight hours, UV index, wind speed, PM2.5, and CO influenced the cumulative pandemic trend in the highlands. The identified influence of environmental factors on SARS-CoV-2 sequence variants adds knowledge of the impact of altitude on COVID-19 infection, offering novel suggestions for preventive intervention.
2024-03-25T00:00:00ZPreparation of a novel metallothionein-AuNP composite material by genetic modification and Au–S covalent combination
http://hdl.handle.net/10547/626173
Preparation of a novel metallothionein-AuNP composite material by genetic modification and Au–S covalent combination
Li, Xuefen; Liu, Hui; Wang, Yuxia; Crabbe, M. James C.; Wang, Lan; Ma, Wenli; Ren, Zhumei
Metallothionein (MTs) can be used in the prevention and treatment of tumors and diabetes due to its antioxidant properties. However, it is necessary to solve its non-transmembrane properties and further improve its antioxidant activity, increase its fluorescence visualization and enhance its stability to meet practical applications in the biomedical field. Here, we report the preparation of a novel metallothionein-AuNP composite material with high transmembrane ability, fluorescence visualization, antioxidant activity, and stability by genetic modification (introducing transduction peptide TAT, fluorescence tag GFP and increasing sulfydryl groups) and immobilization technology (covalently bonding with AuNPs). The transmembrane activity of modified proteins was verified by immunofluorescence. Increasing the sulfhydryl content within a certain range can enhance the antioxidant activity of the protein. In addition, GFP were used to further simplify the imaging of the metallothionein-AuNP composite in cells. XPS results indicated that AuNPs can immobilize metallothionein through Au–S covalent bonds. TGA characterization and degradation experiments showed that thermal and degradation stability of the immobilized material was significantly improved. This work provides new ideas to construct metallothionein composites with high transmembrane ability, antioxidant activity, fluorescence visualization and stability to meet novel applications in the biomedical field.
2024-02-05T00:00:00ZCancer development in hepatocytes by long-term induction of hypoxic hepatocellular carcinoma cell (HCC)-derived exosomes in vivo and in vitro
http://hdl.handle.net/10547/626124
Cancer development in hepatocytes by long-term induction of hypoxic hepatocellular carcinoma cell (HCC)-derived exosomes in vivo and in vitro
Ju, Tuoyu; Dong, Jianjun; Wang, Bowei; Qu, Kaige; Cheng, Can; He, Xiuxia; Tian, Yanling; Crabbe, M. James C.; Wang, Zuobin; Chen, Yujuan
Hypoxic tumor cell-derived exosomes play a key role in the occurrence, development, and metastasis of tumors. However, the mechanism of hypoxia-mediated metastasis remains unclear. In this study, hypoxic hepatocellular carcinoma cell (HCC-LM3)-derived exosomes (H-LM3-exos) were used to induce hepatocytes (HL-7702) over a long term (40 passages in 120 days). A nude mouse experiment further verified the effect of H-LM3-exos on tumor growth and metastasis. The process of cancer development in hepatocytes induced by H-LM3-exos was analyzed using both biological and physical techniques, and the results showed that the proliferation and soft agar growth abilities of the transformed cells were enhanced. The concentration of tumor markers secreted by transformed cells was increased, the cytoskeleton was disordered, and the migration ability was enhanced and was accompanied by epithelial−mesenchymal transition (EMT). Transcriptome results showed that differentially expressed genes between transformed cells and hepatocytes were enriched in cancer-related signaling pathways. The degree of cancer development in transformed cells was enhanced by an increase in H-LM3-exos-induced passages. Nude mice treated with different concentrations of H-LM3-exos showed different degrees of tumor growth and liver lesions. The physical properties of the cells were characterized by
atomic force microscopy. Compared with the hepatocytes, the height and roughness of the transformed cells were increased, while the adhesion and elastic modulus were decreased. The changes in physical properties of primary tumor cells and hepatocytes in nude mice were consistent with this trend. Our study linking omics with the physical properties of cells provides a new direction for studying the mechanisms of cancer development and metastasis.
2023-10-16T00:00:00ZImpacts of marine cloud brightening scheme on climatic extremes in the Tibetan Plateau
http://hdl.handle.net/10547/626123
Impacts of marine cloud brightening scheme on climatic extremes in the Tibetan Plateau
Zhang, Zhihua; Zhu, Yuanzhuo; Crabbe, M. James C.
As an ecologically fragile plateau and major water source in Asia, the Tibetan Plateau (TP) has grown warmer over recent decades, contributing to frequent occurrence of extreme climate events. It is urgently needed to find a suitable option to mitigate climate change impacts in the TP. The marine cloud brightening (MCB) scheme is proposed to mitigate global warming through the increasing cloud droplet number concentration of low marine clouds to reflect some solar radiation back into space. Until now, impacts of MCB scheme on the TP have not been investigated. In this study, we utilized 13 Expert Team on Climate Change Detection and Indices to assess the evolution of climate extremes over the TP with/without MCB implementation. We found that although the MCB is implemented over ocean only, it would cause significant changes on climate extremes in the TP which is very far from oceans and much higher than sea
level. During 2030–2059, MCB implementation can decrease warm temperature extremes, leading to a significant decrease in the TXx index by 6–18°C, the TX90p index by 15–45 days, and the TN90p index by 15–50 days. MCB implementation would also have some cooling effects on cold temperature extremes,
leading to an increase in the ID index by 30–80 days, the TX10p index by 22–32 days, and the TN10p index by about 12 days and a decrease in the TNn index by 0.5–1.5°C. Although MCB implementation
would not have much impacts on precipitation extremes, it would significantly increase the area of the region with <10% drought frequency, and increase the drought intensity in the west of Lhasa city.
2023-09-29T00:00:00Z