bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioproduction of propionic acid using levulinic acid by engineered Pseudomonas putida
Authors: Tiwari Rameshwar , Sathesh-Prabu Chandran , Lee Sung Kuk 
Published: August 2022

The present study elaborates on the propionic acid (PA) production by the well-known microbial cell factory Pseudomonas putida EM42 and its capacity to utilize biomass-derived levulinic acid (LA). Primarily, the P. putida EM42 strain was engineered to produce PA by deleting the methylcitrate synthase (PrpC) and propionyl-CoA synthase (PrpE) genes. Subsequently, a LA-inducible expression system was employed to express yciA (encoding thioesterase) from Haemophilus influenzae and ygfH (encoding propionyl-CoA: succinate CoA transferase) from Escherichia coli to improve the PA production by up to 10-fold under flask scale cultivation. The engineered P. putida EM42:ΔCE:yciA:ygfH was used to optimize the bioprocess to further improve the PA production titer. Moreover, the fed-batch fermentation performed under optimized conditions in a 5 L bioreactor resulted in the titer, productivity, and molar yield for PA production of 26.8 g/L, 0.3 g/L/h, and 83%, respectively. This study, thus, successfully explored the LA catabolic pathway of P. putida as an alternative route for the sustainable and industrial production of PA from LA.
Highly efficient and automated isolation technology for extracellular vesicles microRNA
Authors: Di Kaili , Fan Boyue , Gu Xinrui , Huang Rongrong , Khan Adeel , Liu Chang , Shen Han , Li Zhiyang 
Published: August 2022

MicroRNA (miRNA) in extracellular vesicles (EVs) has great potential to be a promising marker in liquid biopsy. However, the present EV isolation methods, such as ultracentrifugation, have complicated and long-time operation, which impedes research on EV miRNA. The downstream complex miRNA extraction process will also significantly increase the detection cycle and loss. We first established a simple automated technique to efficiently extract target miRNAs in EVs from plasma based on Fe3O4@TiO2 beads with high affinity and capture efficiency. We combined a heat-lysis method for quick and simple EV miRNA extraction and detection. The results indicated that our method has more RNA yield than TRIzol or a commercial kit and could complete EV enrichment and miRNA extraction in 30 min. Through the detection of miRNA-21, healthy people and lung cancer patients were distinguished, which verified the possibility of the application in clinical detection. The automated isolation technology for EV miRNA has good repeatability and high throughput, with great application potential in clinical diagnosis.
Biosynthesis of novel metallic silvers on kraft papers using cephalotaxus harringtonia fruit extract as a sustainable stabilizing agent (KP@AgNP)
Authors: Wei Shaofeng , Liu Xiaoyi , Xie Jiao , Liu Huijuan , Zeng Qibing , wang Guoze , Luo Peng 
Published: August 2022

Greenly synthesized silver nanoparticles (AgNPs) on different cellulosic materials show tremendous potential for colorful, biocidal, and reasonably strong products by replacing the traditional chemical-based synthesis protocols. This study reports on a novel in situ synthesis protocol for synthesizing green and sustainable AgNPs over cellulosic kraft paper substrates using a bio-based stabilizing agent (Cephalotaxus harringtonia fruit extract). The protocol could play a significant role in packaging industries. The aqueous extracts of Cephalotaxus harringtonia fruits have been used to synthesize the metallic silver. The deposited AgNPs values were investigated through XRF (X-ray fluorescence) analysis. The number of deposited nanoparticles (NPs) was 268 ± 7, 805 ± 14, and 1,045 ± 16 PPM, respectively for 0.5, 1.5, and 2.5 mm silver precursors. The developed products were tested with SEM (scanning electron microscopy), SEM-mediated elemental mapping, EDX (energy disruptive X-ray), FTIR (Fourier transform infrared spectroscopy), and XRD (X-Ray diffraction). XRD analysis further confirmed the presence of peaks for elemental AgNP on the deposited papers. Colorimetric values were measured to confirm the colorful appearances of the developed metallic silvers. Mechanical properties were tested in terms of the tensile index and bursting index. Moreover, the statistical analysis of coefficient of variations (R2) and a post-hoc ANOVA test that adopted the Newman-Keul methodology also confirm the significance of developed nanoparticles in the papers. The shielding capacity against UV light was also investigated; all the AgNPs-treated products provided values higher than 40, demonstrating the strong UV resistance capability of the kraft paper material. Overall, the study confirms a successful development of green AgNPs on paper materials.
Characteristics of oral microbiota in plateau and plain youth‐positive correlations between blood lipid level, metabolism and specific microflora in the plateau group
Authors: Zhao LiBo , Wang Huanhuan , Gao Yinghui , Hao Benchuan , Li Xueyan , Wen Ruoqing , Chen Kaibing , Fan Li , Liu Lin 
Published: August 2022

ObjectivesTo analyze the characteristics of oral microbiota in plateau and plain youth and the possible function of the microbiome.Materials and methodsA total of 120 healthy young males (80 on the plateau, 40 on the plain) completed this cross-sectional study. Oral microflora samples were collected from all participants. The bacterial 16S rDNA was amplified using PCR and sequenced using Illumina MiSeq high-throughput sequencing. The data were analyzed to determine the microbial distribution and community structure of the oral microflora from the two groups. Metastats was used to test differences in relative species abundance between the groups. The correlation between the abundance of specific bacteria and blood indicators was also analyzed.ResultsAs demonstrated by alpha and beta diversity, the plateau group had lower microbial richness and a less even distribution of oral microbiota than the plain group. All predominant phyla and genera were qualitatively similar between the two groups, but their relative abundances differed. The relative abundance of bacteria in the phylum Firmicutes was significantly higher in the plateau group than in the plain group. At the genus level, Streptococcus spp. and Gemella spp. were also more abundant in the plateau group. The functional prediction indicated vigorous microbial metabolism in the oral bacterial community. We also found that the relative abundance of Streptococcus spp., the dominant genus, was positively correlated with triglyceride levels in the plateau group.ConclusionsWith increasing altitude, the diversity of oral microbiota and the relative proportion of predominant bacteria were altered. The distribution and related function of Streptococcus spp. were prominent in plateau samples. This comprehensive study of the relationship between oral microecology and elevation provides a point of reference for studying the human body’s adaptability or inadaptability to high altitude.
Exploring the mechanism of action of Xuanfei Baidu granule (XFBD) in the treatment of COVID-19 based on molecular docking and molecular dynamics
Authors: Xiong Li , Cao Junfeng , Yang Xingyu , Chen Shengyan , Wu Mei , Wang Chaochao , Xu Hengxiang , Chen Yijun , Zhang Ruijiao , Hu Xiaosong , Chen Tian , Tang Jing , Deng Qin , Li Dong , Yang Zheng , Xiao Guibao , Zhang Xiao 
Published: August 2022

PurposeThe Corona Virus Disease 2019 (COVID-19) pandemic has become a challenge of world. The latest research has proved that Xuanfei Baidu granule (XFBD) significantly improved patient’s clinical symptoms, the compound drug improves immunity by increasing the number of white blood cells and lymphocytes, and exerts anti-inflammatory effects. However, the analysis of the effective monomer components of XFBD and its mechanism of action in the treatment of COVID-19 is currently lacking. Therefore, this study used computer simulation to study the effective monomer components of XFBD and its therapeutic mechanism.MethodsWe screened out the key active ingredients in XFBD through TCMSP database. Besides GeneCards database was used to search disease gene targets and screen intersection gene targets. The intersection gene targets were analyzed by GO and KEGG. The disease-core gene target-drug network was analyzed and molecular docking was used for verification. Molecular dynamics simulation verification was carried out to combine the active ingredient and the target with a stable combination. The supercomputer platform was used to measure and analyze the number of hydrogen bonds, the binding free energy, the stability of protein target at the residue level, the solvent accessible surface area, and the radius of gyration.ResultsXFBD had 1308 gene targets, COVID-19 had 4600 gene targets, the intersection gene targets were 548. GO and KEGG analysis showed that XFBD played a vital role by the signaling pathways of immune response and inflammation. Molecular docking showed that I-SPD, Pachypodol and Vestitol in XFBD played a role in treating COVID-19 by acting on NLRP3, CSF2, and relieve the clinical symptoms of SARS-CoV-2 infection. Molecular dynamics was used to prove the binding stability of active ingredients and protein targets, CSF2/I-SPD combination has the strongest binding energy.ConclusionFor the first time, it was found that the important active chemical components in XFBD, such as I-SPD, Pachypodol and Vestitol, reduce inflammatory response and apoptosis by inhibiting the activation of NLRP3, and reduce the production of inflammatory factors and chemotaxis of inflammatory cells by inhibiting the activation of CSF2. Therefore, XFBD can effectively alleviate the clinical symptoms of COVID-19 through NLRP3 and CSF2.
Identification of biomarkers, pathways and potential therapeutic agents for salt-sensitive hypertension using RNA-seq
Authors: Chao Xiaoying , Jiang Zhiyuan , Zhong Guoqiang , Huang Rongjie 
Published: August 2022

BackgroundSalt-sensitive hypertension (SSH) is a common type of essential hypertension in China. In recent years, although an increasing number of researches have focused on SSH, few studies have been researched on patients with SSH. The objective of this study was to explore the genes and pathways linked with SSH using RNA-sequencing (RNA-seq).Materials and methodsWe used RNA-seq to analyze the transcriptome of peripheral blood mononuclear cells (PBMCs) of five SSH patients and five SRH patients. Next, we analyzed the differentially expressed genes (DEGs) using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and Gene Set Enrichment (GSEA) enrichment analysis. Then, Cytoscape was used to construct the protein-protein interaction (PPI) network and the hub genes. Finally, CMAP analysis found that several small molecular compounds could reverse the altered DEGs.ResultsA total of 431 DEGs were found in the PBMC samples, including 294 up-regulated and 137 down-regulated genes. Functional enrichment analysis found significant enrichment in immune-related associations such as inflammation, chemokine, and cytokine-cytokine receptor interaction. The hub genes of the two modules were IL-6, IL-1A, CCL2, CCL3L3, and BUB1. In addition, we identified two small molecular compounds (iopromide and iloprost) that potentially interacted with DEGs.ConclusionThis study suggests some potential biomarkers for the diagnosis of SSH. It provides new insights into SSH diagnosis and possible future clinical treatment.
HADH may be the target molecule of early vascular endothelial impairment in T2DM
Authors: Ye Haowen , Wang Ruxin , Wei Jinjing , Wang Ying , Wang Lihong , Zhang Xiaofang 
Published: August 2022

BackgroundType 2 diabetes mellitus (T2DM) will significantly increase the risk of atherosclerosis (AS). Vascular endothelial cell dysfunction (VECD) is the foundation of AS. Early identification and intervention of VECD caused by T2DM can help us effectively delay or even suppress the occurrence of AS.MethodsWe downloaded the gene expression profiles from the Gene Expression Omnibus (GEO). The differential expression genes (DEGs) were identified in R software and weighted gene co-expression network analysis (WGCNA) was performed to further screen the target genes. In addition, we used the receiver operating characteristic curve (ROC curve) to verify the diagnostic efficiency of target genes. Finally, target genes were validated by quantitative polymerase chain reaction (qPCR).ResultsFour target genes (CLUH, COG4, HADH, and MPZL2) were discovered in early vascular endothelial impairment caused by T2DM through differential expression analysis and WGCNA. The ROC curve of target genes showed that HADH had the best diagnostic efficacy in VECD and AS. qPCR showed that the mRNA level expression of HADH and MPZL2 were decreased in human coronary artery endothelial cells (HCAECs) treated with high glucose and palmitic acid.ConclusionHADH may be the target gene in early VECD caused by T2DM.
A possible characteristic of foreshocks derived from the evaluation of loading/unloading induced by earth tides
Authors: Yu Huaizhong , Liu Jie , Ma Yawei , Yan Rui , Yu Chen , Li Shengle , Yang Zhigao , Hong Min , Tu Hongwei , Zhang Zhiwei , Zhao Binbin , Ma Yuchuan 
Published: August 2022

The detection of the potential of a larger event immediately after a moderate earthquake is a quite difficult problem. In this work, we devised an approach to determine whether an earthquake is a foreshock to a larger mainshock by evaluating loading/unloading states. This is done by calculating the Coulomb failure stress (CFS) change induced by Earth tides along the tectonically preferred slip direction on the seismogenic fault surface of each of the candidates. The technique is based on the load/unload response ratio (LURR) method, but the determination of the sliding direction of CFS is different, which is derived from the moderate earthquake that has just occurred rather than the assumption from the regional stress setting. Using the approach, we tested since the year 2000 the Ms ≥ 4.0 foreshocks of the Ms ≥ 6.0 earthquakes on the Chinese mainland, and also the earthquake swarms where no subsequent larger mainshocks were expected in the previous 10 years. The former mostly occurred in the loading process, while the latter arose more frequently in a random process. The marked difference indicates that the occurrence of earthquakes during loading may imply the critical state of the seismogenic faults, and the derived stress is more likely to trigger a larger event than that of the earthquakes that occurred during unloading.
Cdc42 upregulation under high glucose induces podocyte apoptosis and impairs β-cell insulin secretion
Authors: Jiang Shan , Xu Chun-mei , Yao Shuai , Zhang Rui , Li Xian-zhi , Zhang Ru-zhen , Xie Tian-yue , Xing Yi-qian , Zhang Qian , Zhou Xiao-jun , Liao Lin , Dong Jian-jun 
Published: August 2022

ObjectivesThe progressive impairment of β-cell function results in prolonged deterioration in patients with type 2 diabetes mellitus (T2DM). Interestingly, the finding on pancreatitis secondary to renal injury suggests that potential communication exists between kidney and pancreas. Therefore, we aimed to investigate cell division cycle 42 (Cdc42)-mediated podocyte apoptosis and its effect on insulin secretion in islet β-cells.MethodsType 2 diabetic nephropathy mouse models were established to identify the expression of Cdc42 in podocytes by immunohistochemistry. An in vitro co-culture of mouse podocyte MPC5 and β-TC6 cells was preliminarily established. Subsequently, podocyte apoptosis induced by high glucose and Cdc42 was detected by TUNEL staining and western blotting. In addition, the JNK pathway was examined to determine the mechanism of apoptosis in MPC5 cells. Finally, insulin secretion and expression in β-TC6 cells as well as malondialdehyde (MDA) and superoxide dismutase (SOD) levels in both cell types were examined after the regulation of Cdc42 in MPC5 cells.ResultsCdc42 was highly expressed in the podocytes of diabetic nephropathy mice. Exposure to 25 mM glucose for 48 h induced a significant upregulation of Cdc42, Bax, and cleaved caspase-3 as well as a decreased Bcl-2 expression. In addition, marked apoptosis of MPC5 cells was observed compared to normal glucose treatment. After transfection with Cdc42 plasmid, apoptosis of MPC5 cells was enhanced with an increased expression of p-JNK, whereas inhibition of Cdc42 significantly alleviated podocyte apoptosis accompanied by a downregulation of p-JNK. The glucose-stimulated insulin secretion level of β-TC6 cells decreased after the upregulation of Cdc42 in MPC5 cells. Immunofluorescence staining for insulin showed that co-culture with MPC5 cells carrying the Cdc42 plasmid significantly reduced insulin expression, whereas inhibition of Cdc42 in MPC5 cells alleviated the above-mentioned abnormality of β-TC6 cells. The expression of Cdc42 and p-p38 in β-TC6 cells increased following the upregulation of Cdc42 in MPC5 cells; this was concurrent with augmented MDA levels and decreased SOD activity. The opposite result was observed for Cdc42 knockdown in MPC5 cells.ConclusionsCdc42 in podocytes plays a crucial role in insulin secretion by β-cells, which may provide a new therapeutic target to prevent the vicious cycle of β-cell dysfunction in T2DM.
A real-life treatment cohort of pancreatic neuroendocrine tumors: High-grade increase in metastases confers poor survival
Authors: Zhang Wu-Hu , Gao He-Li , Liu Wen-Sheng , Qin Yi , Ye Zeng , Lou Xin , Wang Fei , Zhang Yue , Chen Xue-Min , Chen Jie , Yu Xian-Jun , Zhuo Qi-Feng , Xu Xiao-Wu , Ji Shun-Rong 
Published: August 2022

BackgroundTumor grade determined by the Ki67 index is the best prognostic factor for pancreatic neuroendocrine tumors (PanNETs). However, we often observe that the grade of metastases differs from that of their primary tumors. This study aimed to investigate the frequency of grade changes between primary tumors and metastases, explore its association with clinical characteristics, and correlate the findings with the prognosis.MethodsSix hundred forty-eight patients with pancreatic neuroendocrine neoplasms treated at Fudan University Shanghai Cancer Center were screened for inclusion, and 103 patients with PanNETs who had paired primary tumors and metastases with an available Ki67 index were included. Re-evaluation of Ki67 was performed on 98 available samples from 69 patients.ResultsFifty cases (48.5%) had a Ki67 index variation, and 18 cases (17.5%) displayed a grade increase. Metachronous metastases showed significantly higher Ki67 index variation than synchronous metastases (P=0.028). Kaplan–Meier analyses showed that high-grade metastases compared to low-grade primary tumors were significantly associated with decreased progression-free survival (PFS, P=0.012) and overall survival (OS, P=0.027). Multivariable Cox regression analyses demonstrated that a low-grade increase to high-grade was an unfavorable and independent prognostic factor for PFS and OS (P=0.010, and P=0.041, respectively).ConclusionsA high-grade increase in metastases was an unfavorable predictor of PanNETs, which emphasized the importance of accurate pathological grading and could provide a reference for clinical decision-making.
Inconsistent trends between early and late winters in extreme cold events in China from 1980 to 2021
Authors: Dong Wei , Zhao Liang , Cheng Wei , Guo Chunyan , Shen Xinyong , Yao Haoxin 
Published: August 2022

Understanding intra-seasonal variation in extreme cold events (ECEs) has important implications for climate prediction and climate adaptation. However, the ECEs difference between early (from December 1 to January 15) and late (from January 16 to February 28) winters is a lack of sufficient understanding. Herein, we investigated the trends of ECEs over eastern China in early and late winters. Results showed that the number of days with ECEs had a faster and uniformly decreasing trend in late winter over eastern China, whereas the decreasing trend in early winter was not significant because of the dipole pattern with an increase of ECEs in northeast China and a decrease of ECEs in southeast China during the time period 1980–2021. This denoted that China was presenting a pattern of “cold early winter–warm late winter”. The feature of cold early winter was related to a significant increase in high-latitude blocking highs extending poleward and reaching the Arctic Circle in early winter during the last 20 years. In particular, there was a large-scale tilted high ridge from the Ural Mountains to northern Asia, which favored the negative phase of the Arctic oscillation. This, in turn, led to a strong Siberian high and East Asian winter monsoon. Strong cold advection related to the circulation anomalies caused an ECEs increase in northeast China and dominated the change in temperature over eastern China in early winter. By contrast, the decrease in ECEs in late winter in the last 20 years was more related to the interdecadal enhancement of the anticyclonic anomaly over the north Pacific (NPAC). The strong NPAC extended to East Asia in a zonal direction, causing strong warm anomalies in eastern China through warm advection and diabatic heating, which weakened the northerly and prevented the East Asian trough from moving south, resulting in a warmer East Asia and a uniform decrease in late winter.
Closing county-level yield gaps through better phosphorus fertilizer management in Northeast China
Authors: Shi Wuliang , Zhang Yubin , Peng Mengsu , Shi Yang , Li Wei , Liu Pan , Li Zheng , Song Lixin , Cao Ning , Cui Jinhu , Cui Zhenling 
Published: August 2022

The limited available information on variations in yield gaps (differences between actual yields and the theoretically attainable yields) restricts the development of rational strategies to optimize yields and reduce environmental costs. Quantifying the yield potential and the variations in yield gaps will help identify factors that limit yields and will enable a narrowing of the current yield gap. Here, we applied an analytical framework to yield data to identify options for closing the yield gap at the county level. We used a database containing yields for 40 counties and data from 87 representative on-farm experiments in Jilin Province, China, from 2006 to 2008. The yield potential was simulated for each region-year using a Hybrid-Maize model (http://www.hybridmaize.unl.edu/) and weather data. We then conducted a systematic and spatial analysis of actual yields to identify yield gaps at the county level. The simulated average potential yield at 27 representative sites was 15.2 Mg ha−1 (range 8.1–17.6 Mg ha−1) in Jilin Province. The on-farm experiments suggested an attainable potential yield ranging from 8.7 to 16.7 Mg ha−1 across Jilin Province. During this period, the actual maize yield varied between 4.1 and 11.9 Mg ha−1, according to the county-level data. Farmers’ fields, therefore, achieved 52% of the model yield potential and 77% of the attainable potential yield. Widely different amounts of P fertilizer input among farmers contributed significantly to regional variations in YGE. Soil Olsen-P and rainfall were also major factors. The results indicate that there is great potential to substantially increase the maize yield in non-optimal P management regions, such as in the western Jilin Province. Hence, improvements in regional P management strategies, such as at the county level, need to be assessed separately to provide a basis for increasing the actual maize yield.