bluuebunny/crossref_metadata_2025 huggingface dataset:
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

Purpose

The 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.

Methods

We 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.

Results

XFBD 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.

Conclusion

For 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

Background

Salt-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 methods

We 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.

Results

A 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.

Conclusion

This 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

Background

Type 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.

Methods

We 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).

Results

Four 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.

Conclusion

HADH may be the target gene in early VECD caused by T2DM.
Zonation-based landslide hazard assessment using artificial neural networks in the China-Pakistan Economic Corridor
Authors: Jianqiang Zhang , Yonggang Ge , Yong Li , Qiang Zou , Yuhong Jiang , Huayong Chen , Xiaoqing Chen
Published: August 2022

Distribution of landslide is controlled by various causative factors that have different impacts on the occurrence of landslide in different regions. Using one single model to build the hazard assessment is not enough to fully reflect the spatial differences of landslide controlling factors especially for large area. Landslide hazard assessment based on zonation was therefore proposed in this study with an attempt to take effective measures to address this problem. The China–Pakistan Economic Corridor was taken as the study area where landslide hazard assessment was carried out. Based on the features of geological structure, topography, and climate, the study area was divided into three zones. The controlling factors were further analyzed by the geographical detectors method. It was found that the main controlling factors for landslides in these three zones were related to the site’s topography (altitude, slope gradient, and relief amplitude), land use, and distance to an earthquake epicenter. Furthermore, different factors for landslide hazard assessment were selected based on the result of a controlling factor analysis. An artificial neural network model was employed to build the hazard assessment models, and hazard assessment maps were generated. Validations were conducted, showing that the accuracy of hazard assessment maps by zones was higher than that by the whole study area, despite there was no significant difference during the modeling process.
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

Objectives

The 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.

Methods

Type 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.

Results

Cdc42 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.

Conclusions

Cdc42 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.
Circadian rhythms and pancreas physiology: A review
Authors: Chan Karl , Wong F. Susan , Pearson James Alexander
Published: August 2022

Type 2 diabetes mellitus, obesity and metabolic syndrome are becoming more prevalent worldwide and will present an increasingly challenging burden on healthcare systems. These interlinked metabolic abnormalities predispose affected individuals to a plethora of complications and comorbidities. Furthermore, diabetes is estimated by the World Health Organization to have caused 1.5 million deaths in 2019, with this figure projected to rise in coming years. This highlights the need for further research into the management of metabolic diseases and their complications. Studies on circadian rhythms, referring to physiological and behavioral changes which repeat approximately every 24 hours, may provide important insight into managing metabolic disease. Epidemiological studies show that populations who are at risk of circadian disruption such as night shift workers and regular long-haul flyers are also at an elevated risk of metabolic abnormalities such as insulin resistance and obesity. Aberrant expression of circadian genes appears to contribute to the dysregulation of metabolic functions such as insulin secretion, glucose homeostasis and energy expenditure. The potential clinical implications of these findings have been highlighted in animal studies and pilot studies in humans giving rise to the development of circadian interventions strategies including chronotherapy (time-specific therapy), time-restricted feeding, and circadian molecule stabilizers/analogues. Research into these areas will provide insights into the future of circadian medicine in metabolic diseases. In this review, we discuss the physiology of metabolism and the role of circadian timing in regulating these metabolic functions. Also, we review the clinical aspects of circadian physiology and the impact that ongoing and future research may have on the management of metabolic disease.
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

Background

Tumor 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.

Methods

Six 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.

Results

Fifty 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).

Conclusions

A 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.
The investigation of microporous structure and fluid distribution mechanism in tight sandstone gas reservoirs: A case study on the second member of Xujiahe gas reservoirs in Yuanba area
Authors: Guo Tonglou , Fu Dongyu , Xiong Liang , Wang Yongfei
Published: August 2022

Tight sandstone reservoir is characterized by ultra-low porosity, complex microporous structure and water residues, which shows different gas storage and transport mechanism from conventional reservoirs. Therefore, effective development of tight sandstone gas reservoirs is faced with technical challenges. Microporous structures, distribution mechanism of fluid is a basic issue in gas reservoir evaluation. In this work, we take gas reservoir in the 2nd member of Xujiahe Formation in Yuanba area as an example to analyze the microscopic feature of pore structure and fluid distribution. The three-dimensional digital core has been applied to represent the real microporous structure. Specifically, a digital core reconstruction method based on SEM and casting slice images has been proposed. Ultimately, the mechanism of distribution, mode of occurrence of water residues in tight sandstone reservoirs has been simulated and quantitatively analyzed. The results show that the water residues could been visualized and categorized into three modes, water mass in corner, water film on surface, and water column in throat. The water residues could cause dramatic influence on pore structures, active pore size could be decreased with rising residual water saturation, the magnitude falls by over 50%. In addition, grain size would affect the distribution of water residues, which shows different percentage in medium and fine sand. Pore connectivity is another characteristic factor to describe the microporous structures. In this study, cluster marking algorithm has been applied to obtain the pore connectivity in tight sandstone with different grain size. In medium sand, the pore connectivity is dramatically decreased with rising water saturation, the downward trend become slower when water saturation reaches to 60%. Compared to fine sand, the tendency variation appears when water saturation reaches to 40%. This paper provides an applicable method to reveal the micro-scale reservoir properties and fluid distribution mechanisms in tight sandstone gas reservoirs.
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.
The casual effect of data production factor adoption on company performance: Empirical evidence from Chinese listed companies with PSM-DID
Authors: Guan Rong , Fan Runze , Ren Yi’nuo , Lu Fanyu , Wang Huijuan
Published: August 2022

The usage of data production factor (DPF) has been extensively studied in academic research and industry. The purpose of this study is to examine the causal effects of DPF adoption on company performance. We firstly provide a measurement of DPF adoption by text mining, which is superior to previous studies that use only single metric. Then, based on PSM-DID method, we use the data of China’s listed companies from 2011 to 2019 to identify the causal relationship between data elements adoption and company’s performance. We find that the adoption of DPF can significantly increase companies’ performance. Further heterogeneity tests show that companies from the service industry and state-owned companies achieve a significant improvement in the performance after adopting DPFs in production. Altogether, this study provides the micro evidence on the relationship between the adoption of DPFs and company performance, providing significant implications for the development of digitalization and intelligence production.
Economics of advanced technologies for wastewater treatment: Evidence from pulp and paper industry
Authors: Dagar Sumit , Singh Santosh Kumar , Gupta Manoj Kumar
Published: August 2022

Paper mills generate large quantities of wastewater and sludge waste depending on the type of paper making processes employed. This poses several problems regarding wastewater treatment, discharge, and sludge disposal. Whenever wastewater is generated, it should be treated in wastewater treatment plants prior to being released to the environment since it can be polluting and dangerous. A study was conducted at Star Paper Mills Ltd. Saharanpur, UP to demonstrate the existing and advanced technologies for wastewater treatment. The mill uses woody raw materials such as eucalyptus, poplar, and veener chips to manufacture a wide range of industrial and cultural grade papers, such as absorbent kraft, maplitho, azure lay, and copier. We observed that the most common excess back water is from paper machines, bleach plant effluent, floor cleaning, and other sources of wastewater. High chemical oxygen demand (COD), biochemical oxygen demand (BOD), and low biodegradability are all characteristics of pulp and paper wastewater. Approximately 85–90% of the fresh water utilized is wasted. We examined the wastewater collected and evaluated from the paper mill by Central Pulp and Paper Research Institute (CPPRI). The Effluent treatment plant (ETP) at Star Paper Mills Ltd. is sufficient to facilitate satisfactory removal of suspended matter in clarifiers and oxidation of biodegradable organic matter in aeration tank. As a matter of fact, if the ETP is operated under optimal conditions, the aeration capacity is sufficient to effectively treat even higher BOD loads than the existing load.
The impact of high-tech industry development on energy efficiency and its influencing mechanisms
Authors: Zou Yanfen , Huang Meijuan , Xiang Wenjing , Lu Linzhuo , Lu Yuhai , Gao Jingjing , Cheng Yang
Published: August 2022

In responding to climate change, energy efficiency is one of the key factors for sustainable development, where the high-tech industry can play an important role. However, whether the development of high-tech industry impacts energy efficiency as well as the mechanisms behind still remain unclear. Thus, based on the dynamic spatial Durbin model, this study aims to investigate: 1) the impact of high-tech industry development on energy efficiency from three perspectives of high-tech industry development, i.e., scale, productivity, and agglomeration, and 2) the mechanisms behind such impact especially through technological innovation and industrial structure. The results confirm the influence of high-tech industry development on energy efficiency both directly and indirectly. On the one hand, our analysis contributes on the existing body of scientific knowledge by expounding the relationship between scale, productivity, and agglomeration of high-tech industry development and energy efficiency. On the other hand, it further deepens the understanding on such relationship by revealing two underlying mechanisms behind, i.e., through promoting technological innovation, the productivity and agglomeration of high-tech industries can either completely or partially improve energy efficiency, while the scale and agglomeration of high-tech industries can hinder energy efficiency to a certain level through the industrial restructuring. Based on these findings, this paper provides some policy implications, which are believed to facilitate the practices of energy conservation and emission reduction in China.
Spatial distribution of soil iron across different plant communities along a hydrological gradient in the Yellow River Estuary wetland
Authors: Liu Xue , Sun Dandan , Qin Jifa , Zhang Jiapeng , Yang Yunfei , Yang Jisong , Wang Zhikang , Zhou Di , Li Yunzhao , Wang Xuehong , Ning Kai , Yu Junbao
Published: August 2022

Iron is an important element and its biogeochemical processes are vital to the matter and energy cycles of wetland ecosystems. Hydrology greatly controls characteristics of soil property and plant community in wetlands, which can regulate the behavior of iron and its oxides. However, it remains unclear how the spatial distribution of iron and its forms in estuarine wetlands responses to hydrological conditions. Five typical plant communities along a naturally hydrological gradient in the Yellow River Estuary wetland, including Phragmites australis in freshwater marsh (FPA), Phragmites australis in salt marsh (SPA), Tamarix chinensis in salt marsh (TC), Suaeda salsa in salt marsh (SS) and Spartina alterniflora in salt marsh (SA), as sites to collect soil samples. The total iron (FeT) and three iron oxides (complexed iron, Fep; amorphous iron, Feo; free iron, Fed) in samples were determined to clarify the spatial distribution of iron and explore its impact factors. The mean contents of FeT, Fep, Feo and Fed were 28079.4, 152.0, 617.2 and 8285.3 mg⋅kg–1 of soil at 0–40 cm depth in the different sites, respectively. The means were significantly different across communities along the hydrological gradient, with the higher values for SA on the upper intertidal zone and for SPA on the lower intertidal zone, respectively. Iron and its forms were positively correlated with the total organic carbon (TOC), dissolved organic carbon (DOC), total nitrogen (TN) and clay, and negatively correlated with electrical conductivity (EC). The indexes of iron oxides (Fep/Fed, Feo/Fed and Fed/FeT) were also different across communities, with a higher value for SA, which were positively correlated with soil water content (WC) and TOC. The results indicate that a variety of plant community and soil property derived from the difference of hydrology might result in a spatial heterogeneity of iron in estuarine wetlands.
Comprehensive analysis of molecular features, prognostic values, and immune landscape association of m6A-regulated immune-related lncRNAs in smoking-associated lung squamous cell carcinoma
Authors: Zhang Meng , Zhang Jian , Liu Yang
Published: August 2022

Lung squamous cell carcinoma (LUSC) is the second most common histopathological subtype of lung cancer, and smoking is the leading cause of this type of cancer. However, the critical factors that directly affect the survival rate and sensitivity to immunotherapy of smoking LUSC patients are still unknown. Previous studies have highlighted the role of N6-methyladenosine (m6A) RNA modification, the most common epigenetic modification in eukaryotic species, together with immune-related long non-coding RNAs (lncRNAs) in promoting the development and progression of tumors. Thus, elucidating m6A-modified immune lncRNAs in LUSC patients with smoking history is vital. In this study, we described the expression and mutation features of the 24 m6A-related regulators in the smoking-associated LUSC cohort from The Cancer Genome Atlas (TCGA) database. Then, two distinct subtypes based on the expression levels of the prognostic m6A-regulated immune lncRNAs were defined, and differentially expressed genes (DEGs) between the subtypes were identified. The distributions of clinical characteristics and the tumor microenvironment (TME) between clusters were analyzed. Finally, we established a lncRNA-associated risk model and exhaustively clarified the clinical features, prognosis, immune landscape, and drug sensitivity on the basis of this scoring system. Our findings give insight into potential mechanisms of LUSC tumorigenesis and development and provide new ideas in offering LUSC patients with individual and effective immunotherapies.
Downregulation of miRNA miR-1305 and upregulation of miRNA miR-6785-5p may be associated with psoriasis
Authors: Yan Jianjun , Zhen Yunyue , Wang Ruijie , Li Xueqing , Huang Shan , Zhong Hua , Wen He , Sun Qing
Published: August 2022

Background: The role of serum extracellular vesicles (EVs) is less known in psoriasis.

Objectives: To explore the transcriptomic profile of serum EVs and the potential biomarkers in psoriasis.

Methods: EVs were isolated by differential ultracentrifugation and identified by transmission electron microscope. The diameters of EVs were detected using nanoparticle tracking analysis. Serum EVs-keratinocyte interaction was observed through confocal fluorescence microscopy. miRNA microarray and mRNA microarray were performed in serum EVs (n = 4) and skin lesions (n = 3), respectively. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization were used to detect the expression of miRNAs in serum EVs and skin lesions (n = 15). Bioinformatics analysis was performed to predict the potential target genes and functions of miR-1305 and miR-6785-5p. Western blot, CCK-8 and enzyme-linked immunosorbent assay (ELISA) were used to detect the EVs’ biomarkers, keratinocytes proliferation and cytokines secretion.

Results: A total of 16 miRNAs and 1,725 mRNAs were significantly dysregulated in serum EVs and skin lesions, respectively. miR-1305 was down-regulated and miR-6785-5p was upregulated in both serum EVs and skin lesions. Serum EVs could be taken up by keratinocytes. miR-1305 was downregulated and miR-6785-5p were upregulated in keratinocytes after co-cultured with psoriasis serum EVs compared with controls. Psoriasis serum EVs promoted keratinocyte proliferation and the secretion of CCL20 and IL-8. Serum EVs miR-1305 and miR-6785-5p were associated with disease severity.

Conclusion: Serum EVs might be involved in the activation of keratinocytes through loaded miRNAs in psoriasis. Serum EVs miR-1305 and miR-6785-5p may be associated with psoriasis.
Comprehensive development and validation of gene signature for predicting survival in patients with glioblastoma
Authors: Jin Yi , Wang Zhanwang , Xiang Kaimin , Zhu Yuxing , Cheng Yaxin , Cao Ke , Jiang Jiaode
Published: August 2022

Glioblastoma (GBM) is the most common brain tumor, with rapid proliferation and fatal invasiveness. Large-scale genetic and epigenetic profiling studies have identified targets among molecular subgroups, yet agents developed against these targets have failed in late clinical development. We obtained the genomic and clinical data of GBM patients from the Chinese Glioma Genome Atlas (CGGA) and performed the least absolute shrinkage and selection operator (LASSO) Cox analysis to establish a risk model incorporating 17 genes in the CGGA693 RNA-seq cohort. This risk model was successfully validated using the CGGA325 validation set. Based on Cox regression analysis, this risk model may be an independent indicator of clinical efficacy. We also developed a survival nomogram prediction model that combines the clinical features of OS. To determine the novel classification based on the risk model, we classified the patients into two clusters using ConsensusClusterPlus, and evaluated the tumor immune environment with ESTIMATE and CIBERSORT. We also constructed clinical traits-related and co-expression modules through WGCNA analysis. We identified eight genes (ANKRD20A4, CLOCK, CNTRL, ICA1, LARP4B, RASA2, RPS6, and SET) in the blue module and three genes (MSH2, ZBTB34, and DDX31) in the turquoise module. Based on the public website TCGA, two biomarkers were significantly associated with poorer OS. Finally, through GSCALite, we re-evaluated the prognostic value of the essential biomarkers and verified MSH2 as a hub biomarker.
Transcriptome Profiling to the Effects of Drought Stress on Different Propagation Modes of Tea Plant (Camellia sinensis)
Authors: Ding Zhou , Jiang Changjun
Published: August 2022

Tea plant (Camellia sinensis) is an important economic beverage crop. Drought stress seriously affects the growth and development of tea plant and the accumulation of metabolites, as well as the production, processing, yield and quality of tea. Therefore, it is necessary to understand the reaction mechanism of tea plant under drought conditions and find efficient control methods. Based on transcriptome sequencing technology, this study studied the difference of metabolic level between sexual and asexual tea plants under drought stress. In this study, there were multiple levels of up-regulation and down-regulation of differential genes related to cell composition, molecular function and biological processes. Transcriptomic data show that the metabolism of tea plants with different propagation modes of QC and ZZ is different under drought conditions. In the expression difference statistics, it can be seen that the differential genes of QC are significantly more than ZZ; GO enrichment analysis also found that although differential genes in biological process are mainly enriched in the three pathways of metabolic, single organism process and cellular process, cellular component is mainly enriched in cell, cell part, membrane, and molecular function, and binding, catalytic activity, and transporter activity; the enrichment order of differential genes in these pathways is different in QC and ZZ. This difference is caused by the way of reproduction. The further study of these differential genes will lay a foundation for the cultivation methods and biotechnology breeding to improve the quality of tea.
The prognostic significance of β-Catenin expression in patients with nasopharyngeal carcinoma: A systematic review and meta-analysis
Authors: Zhou Liu-Qing , Shen Jin-Xiong , Zhou Tao , Li Chun-Li , Hu Yao , Xiao Hong-Jun
Published: August 2022

Background:β-Catenin has been recently identified as a promising novel therapeutic target and prognostic marker in different types of cancer. Here, we conduct a meta-analysis to better clarify the correlation between β-Catenin expression and survival outcomes in nasopharyngeal carcinoma (NPC) patients.

Patients/methods: Following the Preferred Reporting Items or Systematic Reviews Meta Analyses (PRISMA) 2020 guidelines, the PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases were systematically searched for relevant studies to explore the prognostic significance of β-Catenin in NPC. Pooled hazards ratios (HRs) and 95% confidence intervals (CIs) were used to estimate the association of β-Catenin expression with survival outcomes in NPC patients. Odd ratios (ORs) and 95% CIs for clinicopathological characteristics were also statistically analyzed.

Results: Eight studies involving 1,179 patients with NPC were ultimately included in the meta-analysis. Pooled analysis indicated that elevated β-Catenin expression was significantly associated with poor OS (HR = 2.45, 95% CIs: 1.45–4.16, p = 0.001) and poor DFS/PFS (HR 1.79, 95% CIs: 1.29–2.49, p = 0.000). Furthermore, β-cadherin was signifcantly associated with higher TMN stages (OR = 5.10, 95% CIs 2.93–8.86, p = 0.000), clinical stages (OR = 5.10, 95% CIs 2.93–8.86, p = 0.000) and lymph node metastasis (LNM) (OR = 5.01, 95% CIs 2.40–10.44, p = 0.000).

Conclusions: This study demonstrated that for NPC, patients with elevated β-Catenin expression are more likely to have poor survival.
The combined prognostic model of copper-dependent to predict the prognosis of pancreatic cancer
Authors: Guan Xiao , Lu Na , Zhang Jianping
Published: August 2022

Purpose: To assess the prognostic value of copper-dependent genes, copper-dependent-related genes (CDRG), and CDRG-associated immune-infiltrating cells (CIC) for pancreatic cancer.

Methods: CDRG were obtained by single-cell analysis of the GSE156405 dataset in the Gene Expression Omnibus (GEO) database. In a ratio of 7:3, we randomly divided the Cancer Genome Atlas (TCGA) cohort into a training cohort and a test cohort. Tumor samples from the GSE62452 dataset were used as the validation cohort. CIBERSORT was used to obtain the immune cell infiltration. We identified the prognostic CDRG and CIC by Cox regression and the least absolute selection operator (LASSO) method. The clinical significance of these prognostic models was assessed using survival analysis, immunological microenvironment analysis, and drug sensitivity analysis.

Results: 536 CDRG were obtained by single-cell sequencing analysis. We discovered that elevated LIPT1 expression was associated with a worse prognosis in pancreatic cancer patients. EPS8, CASC8, TATDN1, NT5E, and LDHA comprised the CDRG-based prognostic model. High infiltration of Macrophages.M2 in pancreatic cancer patients results in poor survival. The combined prognostic model showed great predictive performance, with the area under the curve (AUC) values being basically between 0.7 and 0.9 in all three cohorts.

Conclusion: We found a cohort of CDRG and CIC in patients with pancreatic cancer. The combined prognostic model provided new insights into the prognosis and treatment of pancreatic cancer.
Mast cells and tryptase are linked to itch and disease severity in mycosis fungoides: Results of a pilot study
Authors: Terhorst-Molawi Dorothea , Lohse Katharina , Ginter Katharina , Puhl Viktoria , Metz Martin , Hu Man , Maurer Marcus , Altrichter Sabine
Published: August 2022

Introduction

In mycosis fungoides (MF), the most common cutaneous T-cell lymphoma, itch is a frequent clinical symptom. Whether mast cells (MCs), eosinophils (Eos) or their mediators play a role in MF-associated itch or disease severity is controversially discussed. Here, we explored the role of MC and Eo numbers in the skin as well as blood levels of their mediators in disease severity and itch.

Methods

In 10 patients with MF and 10 matched control subjects we assessed disease severity, itch, and quality of life impairment using dedicated tools such as the mSWAT, ItchyQoL and DLQI. We analyzed skin biopsies and measured serum levels of tryptase, a mast cell mediator, as well as of the eosinophil products eosinophil cationic protein (ECP) and major basic protein (MBP).

Results

The presence of chronic itch, in four of 10 patients, was associated with significantly higher disease severity (mSwat), larger body surface area affected, and stronger QoL impairment (Itchy-Qol, DLQI). Serum levels of tryptase, but not ECP and MBP, were linked with patient-reported disease severity, body surface area affected, and the presence of itch. Three of the four patients with chronic itch, but none of the six patients without, had tryptase levels above >6µg/l. Numbers of MCs in the papillary dermis were higher in MF skin lesions then in non-lesional skin of MF patients and skin of healthy controls.

Discussion

The MC-mediator tryptase, in MF, is linked to disease activity and impact, most prominently to itch. Our findings call for larger studies that explore the role of MCs, tryptase and other MC mediators as drivers of itch and their role in MF pathogenesis.
The immune phenotypes and different immune escape mechanisms in colorectal cancer
Authors: Mao Yihao , Xu Yuqiu , Chang Jiang , Chang Wenju , Lv Yang , Zheng Peng , Zhang Zhiyuan , Li Zhiqiang , Lin Qi , Tang Wentao , Zhu Dexiang , Ji Meiling , He Guodong , Feng Qingyang , Xu Jianmin
Published: August 2022

The tumor microenvironment (TME) plays a crucial role in tumor progression and metastasis. However, the immune phenotypes of colorectal cancer (CRC) and the underlying immune escape mechanism have not been studied sufficiently. A total of 1802 and 619 CRC samples from the microarray and TCGA cohorts were enrolled, respectively. The ssGSEA algorithm and unsupervised clustering were used for TME cell infiltration speculation and immune phenotype recognition in the above cohorts. A total of 447 samples from Zhongshan Hospital were collected for validation. Immunohistochemistry was performed in this cohort to quantify TME cell infiltration. The single-cell RNA-seq (scRNA-seq) data of 252,940 cells from 60 CRC samples was analyzed for further mechanistic exploration. CRC samples can be classified into three distinct immune phenotypes. Subtype 1, the immune-active subtype, was characterized by high infiltration of activated adaptive immune cells. Subtype 2, the immune-desert subtype, featured high tumor purity and low infiltration of immune and stromal cells. Subtype 3, the stroma-rich subtype, had high infiltration of stromal cells. The stroma-rich subtype conferred a significantly worse prognosis. The three subtypes had different immune escape mechanisms. The immune-active subtype has the highest immune checkpoint expression level. In comparison, the immune-desert subtype had the lowest immunogenicity and defective antigen presentation. The stroma-rich subtype lacked activated immune cells. In conclusion, distinct immune phenotypes and immune escape mechanisms may provide inspiration and direction for further research on CRC immunotherapy.
Boosting regulatory T cell function for the treatment of autoimmune diseases – That’s only half the battle!
Authors: Schlöder Janine , Shahneh Fatemeh , Schneider Franz-Joseph , Wieschendorf Björn
Published: August 2022

Regulatory T cells (Treg) represent a subset of specialized T cells that are essential for the regulation of immune responses and maintenance of peripheral tolerance. Once activated, Treg exert powerful immunosuppressive properties, for example by inhibiting T cell-mediated immune responses against self-antigens, thereby protecting our body from autoimmunity. Autoimmune diseases such as multiple sclerosis, rheumatoid arthritis or systemic lupus erythematosus, exhibit an immunological imbalance mainly characterized by a reduced frequency and impaired function of Treg. In addition, there has been increasing evidence that – besides Treg dysfunction – immunoregulatory mechanisms fail to control autoreactive T cells due to a reduced responsiveness of T effector cells (Teff) for the suppressive properties of Treg, a process termed Treg resistance. In order to efficiently treat autoimmune diseases and thus fully induce immunological tolerance, a combined therapy aimed at both enhancing Treg function and restoring Teff responsiveness could most likely be beneficial. This review provides an overview of immunomodulating drugs that are currently used to treat various autoimmune diseases in the clinic and have been shown to increase Treg frequency as well as Teff sensitivity to Treg-mediated suppression. Furthermore, we discuss strategies on how to boost Treg activity and function, and their potential use in the treatment of autoimmunity. Finally, we present a humanized mouse model for the preclinical testing of Treg-activating substancesin vivo.