bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum α-KL, a potential early marker of diabetes complications in youth with T1D, is regulated by miRNA 192
Authors: Gong Zhenwei , Banchs Pedro A. Pagán , Liu Ye , Fu Haoyi , Arena Vincent C. , Forno Erick , Libman Ingrid , Ho Jacqueline , Muzumdar Radhika
Published: August 2022

Despite the wealth of information on biomarkers of diabetes complications in adults with type 1 diabetes, data in the pediatric population is limited. Diabetic nephropathy (DN), the leading cause of mortality in type 1 diabetes T1D), could be potentially missed in youth, as albuminuria, the current “gold” standard, may be transient and may not reflect permanent renal impairment. Soluble alpha KL has emerged as a potential marker of early diabetic nephropathy. Seventy-nine pediatric patients with type 1 diabetes meeting ISPAD criteria for nephropathy screening were consecutively recruited (90% Caucasian, 51% male, mean age 16.1 ± 3.1 years, duration of T1D 7.2 ± 3.9 years, 2-year average HbA1c 8.0 ± 1.3%, and serum and urine samples were collected for analysis. Serum Klotho (KL) and circulating miRNA levels of select miRNA involved in the pathogenesis of DN were estimated. KL had a strong inverse correlation with diabetes duration and HbA1c, two important risk factors in the development of diabetes complications. Serum miR-192 were negatively associated with KL among children with prolonged duration of diabetes (≥12 years) after adjustment for age and sex. In cell culture, overexpression of miR-192 significantly downregulated KL mRNA and protein levels, and reduced KL levels in the media. miR-192 mimic reduced luciferase activity in a reporter containing the KL 3’ UTR (60% compared to controls, p<0.01), and the inhibitor rescued it. Deletion of a potential binding site for miR-192 in the KL 3’UTR completely abolished the effect of miR-192 in the reporter assay, suggesting that KL is a direct target gene of miR-192. Overexpression of miR-192 significantly increased oxidative stress (MDA) and expression of inflammatory and senescence markers IL-6 and p16. Inhibition of miR-192 significantly reduced levels of MDA, IL-6 and p16. In summary, we demonstrate an increase in miR-192 and a decrease in KL levels in children with prolonged duration of T1D. We demonstrate a novel role for miR-192 in directly regulating KL levels, and through that, senescence and oxidative stress, key pathological processes in the development of DN. miR-192 and/or KL levels are altered with severity and duration of diabetes and could serve as early biomarkers for DN.
Comparison of clinicopathological features and prognosis of papillary thyroid carcinoma and microcarcinoma: A population-based propensity score matching analysis
Authors: Qian Bei , Hu Longqing , Zhang Shoupeng , Zhu Junlin , Mei Li , Huang Tao , Qu Xincai
Published: August 2022

Background

Overtreatment of papillary thyroid microcarcinoma (PTMC) has become a common concern. This study aimed to compare clinicopathological features between PTMC and papillary thyroid carcinoma (PTC) and to explore whether surgery can confer significant survival benefits in all patients with PTC or PTMC.

Methods

Data of 145,951 patients with PTC registered in Surveillance, Epidemiology, and End Results (SEER) database and 8,751 patients with PTC in our institution were retrospectively collected. Patients with tumors less than 10 mm in diameter were classified as PTMC cohort and the rest as PTC cohort. Clinicopathological features between PTMC and PTC were compared on the basis of SEER cohort and validated with institutional data. Survival analysis was conducted to explore the effect of surgery on the prognosis of patients. To minimize potential confounders and selection bias, we performed propensity score matching (PSM) analysis to match more comparable cohorts.

Results

Compared with PTC, PTMC exhibited the following characteristics: more common in women and whites, older age at diagnosis, lower proportion of follicular variants, intraglandular dissemination, extraglandular and capsular invasion, higher proportion of multifocality, fewer lymph node and distant metastases, and higher cancer-specific survival (CSS) and overall survival (OS) (all p-value < 0.05). Regarding treatment, patients with PTMC received a lower proportion of radiotherapy, chemotherapy, and total thyroidectomy but a higher proportion of lobectomy and/or isthmectomy. There was no significant difference in CSS for patients with PTMC at stage T1N0M0 with or without surgery (P = 0.36).

Conclusion

Generally, PTMC showed higher biological indolence than PTC, which meant a higher survival rate for patients in both OS and CSS. For patients with PTMC at staged T1N0M0, active surveillance (AS) may be a potentially feasible management strategy. However, the maintenance of good medical compliance and the management of psychological burden cannot be ignored for patients included in AS.
The roles of circRNA–miRNA–mRNA networks in the development and treatment of osteoporosis
Authors: Gao Manqi , Zhang Zhongkai , Sun Jiabin , Li Bo , Li Yuan
Published: August 2022

Osteoporosis is a systemic metabolic disease, mainly characterized by reduced bone mineral density and destruction of bone tissue microstructure. However, the molecular mechanisms of osteoporosis need further investigation and exploration. Increasing studies have reported that circular RNAs (circRNAs), a novel type of RNA molecule, play crucial roles in various physiological and pathological processes and bone-related diseases. Based on an in-depth understanding of their roles in bone development, we summarized the multiple regulatory roles and underlying mechanisms of circRNA–miRNA–mRNA networks in the treatment of osteoporosis, associated with bone marrow mesenchymal stem cells (BMSCs), osteoblasts, and osteoclasts. Deeper insights into the vital roles of circRNA–miRNA–mRNA networks can provide new directions and insights for developing novel diagnostic biomarkers and therapeutic targets in the treatment of osteoporosis.
In silico identification and verification of ferroptosis-related genes in type 2 diabetic islets
Authors: Yin Meiqi , Zhou Liang , Ji Yanan , Lu Rongxin , Ji Wei , Jiang Guorong , Ma Jin , Song Xiudao
Published: August 2022

Type 2 diabetes (T2D) is a major global public health burden, with β-cell dysfunction a key component in its pathogenesis. However, the exact pathogenesis of β-cell dysfunction in T2D is yet to be fully elucidated. Ferroptosis, a recently discovered regulated form of non-apoptotic cell death, plays a vital role in the development of diabetes and its complications. The current study aimed to identify the key molecules involved in β-cell ferroptosis3 in patients with T2D using the mRNA expression profile data of GSE25724 by bioinformatic approaches. The differentially expressed mRNAs (DE-mRNAs) in human islets of patients with T2D were screened using the islet mRNA expression profiling data from the Gene Expression Omnibus and their intersection with ferroptosis genes was then obtained. Ferroptosis-related DE-mRNA functional and pathway enrichment analysis in T2D islet were performed. Using a protein-protein interaction (PPI) network constructed from the STRING database, Cytoscape software identified ferroptosis-related hub genes in the T2D islet with a Degree algorithm. We constructed a miRNA-hub gene network using the miRWalk database. We generated a rat model of T2D to assess the expression of hub genes. A total of 1,316 DE-mRNAs were identified in the islet of patients between T2D and non-T2D (NT2D), including 221 and 1,095 up- and down-regulated genes. Gene set enrichment analysis revealed that the ferroptosis-related gene set was significantly different in islets between T2D and NT2D at an overall level. A total of 33 ferroptosis-related DE-mRNAs were identified, most of which were significantly enriched in pathways including ferroptosis. The established PPI network with ferroptosis-related DE-mRNAs identified five hub genes (JUN, NFE2L2, ATG5, KRAS, and HSPA5), and the area under the ROC curve of these five hub genes was 0.929 in the Logistic regression model. We constructed a regulatory network of hub genes and miRNAs, and the results showed that suggesting that hsa-miR-6855-5p, hsa-miR-9985, and hsa-miR-584-5p could regulate most hub genes. In rat model of T2D, the protein expression levels of JUN and NFE2L2 in pancreatic tissues were upregulated and downregulated, respectively. These results contribute to further elucidation of ferroptosis-related molecular mechanisms in the pathogenesis of β-cell dysfunction of T2D.
Pyroptosis and inflammasomes in diabetic wound healing
Authors: Mu Xingrui , Wu Xingqian , He Wenjie , Liu Ye , Wu Faming , Nie Xuqiang
Published: August 2022

Diabetic wound is one of the complications of diabetes and is not easy to heal. It often evolves into chronic ulcers, and severe patients will face amputation. Compared with normal wounds, diabetic wounds have an increased proportion of pro-inflammatory cytokines that are detrimental to the normal healing response. The burden of this disease on patients and healthcare providers is overwhelming, and practical solutions for managing and treating diabetic wounds are urgently needed. Pyroptosis, an inflammatory type of programmed cell death, is usually triggered by the inflammasome. The pyroptosis-driven cell death process is primarily mediated by the traditional signaling pathway caused by caspase -1 and the non-classical signaling pathways induced by caspase -4/5/11. Growing evidence that pyroptosis promotes diabetic complications, including diabetic wounds. In addition, inflammation is thought to be detrimental to wound healing. It is worth noting that the activation of the NLRP3 inflammasome plays a crucial role in the recovery of diabetic wounds. This review has described the mechanisms of pyroptosis-related signaling pathways and their impact on diabetic wounds. It has discussed new theories and approaches to promote diabetic wound healing, as well as some potential compounds targeting pyroptosis and inflammasome signaling pathways that could be new approaches to treating diabetic wounds.
A bibliometric and visualization analysis of glucocorticoid-induced osteoporosis research from 2012 to 2021
Authors: Jiang Buchan , Feng Chengyao , Li Chenbei , Tu Chao , Li Zhihong
Published: August 2022

Introduction

Glucocorticoid-induced osteoporosis (GIOP) is the most common cause of secondary osteoporosis. Although many studies related to GIOP have been published, there was no bibliometric analysis in this field. This study aimed to investigate the research trends on GIOP by using bibliometric analysis.

Materials and Methods

All data were collected from the Web of Science Core Collection (WoSCC). All original research articles regarding GIOP from 2012 to 2021 were retrieved. CiteSpace was used to analyze the distribution of countries, institutions, journals, authors, and keywords. We revealed hotspots and trends in the field by drawing co-occurrence keyword maps and identifying burst keywords.

Results

From 2012 to 2021, 685 relevant articles were published, with a peak in 2018 in the annual number of publications. China and McMaster University were the leading country and institution in this field with 208 and 12 publications, respectively. Osteoporosis International was the journal with the most studies, while Journal of Bone and Mineral Research was the most cited journal. “Bone mineral density”, “fracture”, “postmenopausal women”, “prevention” and “therapy” were the most high-frequency keywords, while “bone mineral density”, “bisphosphonate” and “metabolism” were the top high-centrality keywords.

Conclusion

The results from this bibliometric study provided insight into the status and research trends in GIOP of the past decade, which could help researchers quickly determine the current hotspots and frontier trends in this field.
Dendrobium officinale polysaccharide ameliorates polycystic ovary syndrome via regulating butyrate dependent gut–brain–ovary axis mechanism
Authors: Feng Xueping , Wang Decai , Hu Linlin , Lu Haishan , ling Bo , Huang Yanna , Jiang Qinyang
Published: August 2022

Research has shown that dendrobium officinale polysaccharide (DOP) can promote follicular development and inhibit the apoptosis of ovarian granular cells in PCOS rats. However, DOP cannot be absorbed directly by the stomach and small intestine but is degraded into short-chain fatty acids by gut microbiota in the large intestine and regulates the composition of gut microbiota. How DOP improved ovarian function in PCOS rats through the blood–brain barrier is unclear. In this study, we generated letrozole-induced PCOS rat models and studied the therapeutic effect and mechanism of DOP. 16S rRNA amplicon sequencing analysis, GC-MS short-chain fatty acid detection, and Gene Expression Omnibus database searching were conducted to screen the significantly changed pathways, and a series of experiments, such as enzyme-linked immunosorbent assay, RT-qPCR, Western blot, and immunohistochemistry, were performed. We found that DOP treatment could improve ovarian morphology and endocrine disorders, restore the normal estrus cycle, increase gut microbiota α diversity, and alter β diversity and enrichment of butyrate-producing bacterium in PCOS rats. In addition, compared with PCOS rats, those treated with DOP exhibited higher butyrate and polypeptide YY levels, possibly due to the regulation of G protein-coupled receptor 41 expression. These results indicated that DOP relieved the symptoms of PCOS rats which may be related to the mechanism of butyrate dependent gut–brain–ovary axis protection.
Identification of the alpha linolenic acid metabolism-related signature associated with prognosis and the immune microenvironment in nasopharyngeal carcinoma
Authors: Fang Zhijie , Huang Hua , Wang Liyu , Lin Zhiqiang
Published: August 2022

Background

Tumor metabolism is important for cancer progression. Nevertheless, the role of the metabolism pathway and related molecules in nasopharyngeal carcinoma (NPC) is limited.

Methods

Open-accessed data was downloaded from The Cancer Genome Atlas database. All the analysis was performed using the R software and the package in R environments.

Results

In our study, we firstly explored the role of 21 metabolism-related pathways in NPC patients. We found that the steroid biosynthesis and biosynthesis of unsaturated fatty acids were risk factors, while the alpha linolenic acid metabolism was a protective factor. Then, the alpha linolenic acid metabolism aroused our interest. A total of 128 differentially expressed genes (DEGs) were identified, including 71 downregulated and 57 upregulated genes identified between high and low alpha linolenic acid metabolism level. Based on these DEGs, we constructed a prognosis model including DEFB4B, FOXL2NB, MDGA2, RTL1, SLURP2, TMEM151B and TSPAN19, which showed great prediction efficiency in both training and validation cohorts. Clinical correlation analysis showed that high-risk patients might have worse clinical pathology parameters. Pathway enrichment analysis showed that riskscore was positively correlated with angiogenesis, DNA repair, G2/M checkpoints, IL6/JAK/STAT3 signaling, KRAS signaling up, WNT beta-catenin signaling, PI3K/AKT/mTOR signaling, yet positively correlated with inflammatory response, xenobiotic metabolism, TNF-α signaling via NFKB and interferon-gamma response. Immune infiltration analysis showed that the riskscore was positively correlated with the M2 and M0 macrophages, but negatively correlated with neutrophils, plasma cells, follicular helper T cells and resting dendritic cells Moreover, we found that the low-risk patients might be more sensitive to immunotherapy and lapatinib.

Conclusions

In all, our study identified the genes associated with alpha linolenic acid metabolism and constructed an effective prognosis model which could robustly predict NPC patients prognosis.
Review of Unconventional Natural Gas Liquefaction Processes
Authors: Xu Jingxuan , Lin Wensheng , Chen Xi , Zhang Hua
Published: August 2022

Liquefied natural gas (LNG) has become an important part in the energy industry on account of its high energy density, low carbon emission, and convenient transportation. In recent years, with the discovery of unconventional natural gas resources, the situation of the world’s natural gas liquefaction plants using conventional natural gas as feedstock is changing. Unlike traditional LNG plants, unconventional natural gas liquefaction processes require special considerations in design and manufacturing. This review summarizes and analyzes the characteristics and differences of several typical unconventional natural gas liquefaction processes compared to traditional natural gas liquefaction processes, including coalbed methane liquefaction, synthetic natural gas liquefaction, LNG-FPSO, and PLNG (pressurized liquefied natural gas). Moreover, a state-of-the-art review of the recent progress on design and optimization of unconventional natural gas liquefaction processes is presented.
Numerical Investigation on Aerodynamic Performances of the Single-Stage Transonic Turbine With Various Coolant Ejection Positions and Coolant Mass Flow Rates
Authors: Zhang Jinming , Zhou Xun , Du Wei , Xu Senpei
Published: August 2022

The effects of film cooling holes on the suction surface and the coolant mass flow were studied in this research, which focused on load distribution and flow characteristics such as shock migration. A high and low degree of reaction scheme (degree of reaction = 0.3, 0.53) is selected to numerically investigate the aerodynamic performance with consideration of air film cooling. The results show that the above factors have different influences on the intensity and the trailing edge shock direction. The reflected shock weakens and then recovers when the coolant ejection position approaches and departs from the reflection point. Altering the coolant ejection position or coolant mass flow rate mainly affects the load at the front and middle of the blade and has some effects on the pressure rise at the trailing edge as well. There is an optimal position (x/Cax = 0.6) and optimal coolant volume (10% mainstream mass flow rate) for flattening the pressure rise and weakening shocks, thereby reducing losses.
Sizing of centralized shared energy storage for resilience microgrids with controllable load: A bi-level optimization approach
Authors: Du Xili , Li Xiaozhu , Hao Yibo , Chen Laijun
Published: August 2022

To improve the utilization of flexible resources in microgrids and meet the energy storage requirements of the microgrids in different scenarios, a centralized shared energy storage capacity optimization configuration model for microgrids based on bi-level optimization is proposed. First, the response characteristics of the shared energy storage and controllable load in the resilience microgrid are analyzed, and the centralized shared energy storage operation mode meeting the regulatory demand of multi-scenarios is designed. Then, a bi-level optimal allocation model is constructed, which takes the maximum net income of centralized shared energy storage as the upper layer and the minimum payment cost of load in the microgrid as the lower layer. Furthermore, the multi-objective whale optimization algorithm is used to solve the bi-level optimization model. The results show that the shared energy storage can jointly meet the regulation demand of multi-scenarios by coordinating the transferable load and cuttable load in the microgrid and improving the utilization rate of shared energy storage.
Operational risk allocation in urban rail transit public–private partnership projects
Authors: Xiang Pengcheng , Zhang Qianman , Jiang Qiuyan , Liu Zhaowen
Published: August 2022

Operation risk (OR) has affected sustainable development of urban rail transit (URT) public–private partnership (PPP) projects in China. Balanced distribution of operational risks among stakeholders (the public, government, and private companies) involved in URT PPP projects can maximize overall profit. Quantitative analysis of operational risk allocation of urban rail transit PPP project is the key to achieve balance. Few existing studies have quantitatively analyzed operation risk allocation (ORA) in URT PPP project. The objective of this research is to construct a quantitative risk allocation model among three participants by using cooperative game theory. The risk allocation model was modified based on the consideration of four factors affecting the allocation of operational risks: controllability, risk loss, affordability, and handling cost. A case was used as an empirical example, and possible problems were illustrated. The result shows it is necessary and feasible to let the public bear part of the operational risk of the project by raising ticket prices. The results reveal that the public will play an important role in balancing risk allocation. This study shows that an ORA model can suggest how to make the risk allocation process more reasonable, fair, and stable. Meanwhile, the quantitative approach proposed can also be used by stakeholders in achieving fairness and stability of the partnership.
International research progress and trend of transit-oriented development: An analysis of knowledge mapping based on cite space
Authors: Wu Tao , Li Mingjing
Published: August 2022

Transit-oriented development (TOD) which is regarded as one of the most successful planning methods for urban and transport sustainability, has garnered much attention from academics and planners. Despite the growing interest in TOD research, there has not been a comprehensive review of the knowledge structure, research hotspots and emerging trends about TOD research. This study aims to address the research gap by providing a bibliometric overview and visualization of the TOD research. Based on the bibliometric analysis methods, this study uses data collected from Web of Science (WOS) and uses CiteSpace software for visualizing and analyzing international research progress and trends in the TOD field. The results showed that publications on TOD research increased significantly, and most of the articles were published by the United States and China. Universities were the mainstays of the TOD research institutions, and the most productive authors were Dr. Ewing, Dr. Cervero, and Dr. Bertolini. The co-citation network analysis showed that the influential articles were published by Kamruzzaman, Vale, and Papa, and six main research area could be detected. The keyword co-occurrence network analysis displayed three stages for the evolution of TOD research, and popular topics in different stages were revealed. Three Frontier hotspots were identified by the keywords burst analysis, namely oriented development, pattern, and typology.
Global value chain participation impacts carbon emissions—Take the electro-optical equipment industry as an example
Authors: Ma Xiaoming , Liu Xin , Pan Xiaoli , Liao Xiawei
Published: August 2022

This study selects the electro-optical equipment manufacturing industry as an example to explore whether participation in the global value chain increases or mitigates a country’s carbon emissions and describes the impacting factors. Based on multi-regional input-output tables, a value-added decomposition model is used to decompose forward and backward value-added/final products of the world’s electro-optical equipment manufacturing industries in 65 countries from 2005 to 2015. Impacts of several global value chain participation characteristics, including position, forward participation and production length, and backward participation and production length, on a country’s carbon emissions, are examined. The results show that Asian countries have the highest participation rate in the global value chain, both forward and backward, of the electro-optical equipment sector with increasing proportions for forward participation, but lowest backward participation, in simple global value chains. An increase in forward global value chain participation contributes to the reducing carbon emission intensity of the electro-optical equipment manufacturing industry, particularly in terms of simple global value chain participation. On the other hand, the production length of the backward simple global value chain is positively correlated with the total imported carbon emission intensity, indicating that the longer the simple global value chain of foreign production is included in the industry’s imported intermediate products and the lower the country’s position in the global value chain is, the higher its imported carbon emission intensity is. Upgrade in the global value chain is able to reduce the embodied carbon emissions in the intermediate product exports and total imports.
Effect of different biochar particle sizes together with bio-organic fertilizer on rhizosphere soil microecological environment on saline–alkali land
Authors: Gu Yin-yu , Zhang Hai-yang , Liang Xiao-yan , Fu Rao , Li Meng , Chen Chuan-jie
Published: August 2022

The application of biochar and bio-organic fertilizers (BOFs) is effective for improving soil ecological environments. However, soil physicochemical properties and the microbiome diversity of rhizosphere soil after the application of different-sized particles of biochar together with BOF in saline–alkali land have not been thoroughly described. A field experiment was performed to investigate the effects of different-sized particles of apple shoot biochar (60, 30, and 10 mesh) together with BOF on soil bacteria (using Illumina high-throughput sequencing) and the physicochemical properties of Mesembryanthemum cordifolium L. f. grown on saline–alkali land. Results indicated that the combined application of BOF and 10–60 mesh biochar reduced the volumetric weight of soil by 14%–29%, respectively, and additionally decreased soil electrical conductivity, increased the aerial biomass of the M. cordifolium L. f. by over 30%, and notably improved soil water–holding capacity, with 60 mesh giving the best results; organic carbon (OC), organic matter (OM), total nitrogen (N), available phosphorus, alkaline nitrogen, total potassium (K), and total phosphorus (P) were all significantly increased by the addition of combined biochar and BOF; thereinto, field capacity, N, P, K, OC, and OM were positively correlated with the bacterial community structure of coapplied biochar and BOF. There were no significant differences in the richness of total bacteria among the treatments; Proteobacteria, Actinobacteria, and Chloroflexi accounted for >70% of the total bacteria in each treatment; Norank_f__Geminicoccaceae and Micromonospora were the dominant genera across the treatments. The findings suggested that plant growth, physicochemical properties, and community diversity of rhizosphere bacteria in saline–alkali land were significantly positively influenced by biochar 60 mesh plus BOF, followed by biochar 10 and 30 mesh plus BOF. This conclusion could facilitate the study of the ecological functions of biochar and BOF, as well as their interactions with salt-tolerant plants on saline–alkali soil, which can be used to provide exploration ideas for saline–alkali land improvement.
Coupling driving factors of eco-environmental protection and high-quality development in the yellow river basin
Authors: Xin Yun , Liu Xiaoyu
Published: August 2022

Most cities in the Yellow River Basin are located in the central and western regions of China. Restricted by historical evolution, natural environment, resource endowments and other conditions, the economic and social development model of the Yellow River Basin region is outdated, and the level of economic and social development is relatively lagging, which hinders its coordinated development of ecology and economy. This paper uses the coupling coordination degree model, GIS spatial analysis method, NAR neural network model, spatial autoregression, and geographically weighted regression model to investigate the coupling coordination level, spatial differentiation characteristics, future development trend, and coupling driving factors of eco-environmental protection and high-quality development in the Yellow River Basin. The results show that From 2003 to 2018, the level of eco-environmental protection and high-quality development in most areas of the Yellow River Basin gradually improved, presenting a spatial imbalance characteristic of “high in the east and low in the west. The coupling coordination degree of eco-environmental protection and high-quality development in various regions of the Yellow River Basin increased year by year during the survey period. In 2018, most cities had been transformed into intermediate coordinated development areas, and most cities in Inner Mongolia and the middle and lower reaches south of the Yellow River have been upgraded to a well-coordinated development stage. The coupled and coordinated development relationship between eco-environmental protection and high-quality development in the Yellow River Basin has significant spatial agglomeration characteristics, and the local spatial positive correlation gradually increases. From 2019 to 2023, the average level of coupling coordination between eco-environmental protection and high-quality development in the Yellow River Basin during the forecast period is 0.802, 0.807, 0.809, 0.813, and 0.816, respectively, all of which have entered a stage of well-coordinated development. The coupled driving factors of ecological protection and high-quality development in the Yellow River Basin are ranked from strong to weak: energy utilization, urbanization, water resources development, and industrialization. Among them, the degree of energy utilization is the root of the differentiation of coupling coordination between eco-environmental protection and high-quality development in 74 regions of the Yellow River Basin. This study puts forward two strategic suggestions based on the optimal utilization strategy of energy and water resources and the coordinated promotion strategy of industrialization and urbanization, which has great practical and scientific significance for promoting the coordinated development of ecological environment protection and high-quality development in the Yellow River Basin.
The effects of drought on stock prices: An industry-specific perspective
Authors: Cheng Xinbin , Wang Yudong , Wu Xi
Published: August 2022

In this study, we examine the effect of drought on industry stock prices using a balanced panel of monthly data for 15 industries classified by China Securities Regulatory Commission in 2012. By combining the results of ordinary least squares (OLS) estimation and quantile regression models, we present a comprehensive evaluation of the relationship between drought and industry stock prices. The OLS regression results generally show that drought is negatively correlated with industry stock prices. However, quantile regression reveals that the effect of drought changes from positive to negative from the lowest to the highest stock price quantile. In addition, drought resistance capacity varies by industry. We further use threshold regression to determine the effects of investor sentiment on the relationship between drought and stock prices and identify two different regimes: low sentiment and high sentiment. In the low sentiment regime, drought has a significant negative effect on industry stock prices, while in the high sentiment regime, drought has a significant positive impact on industry stock prices.
Pan-cancer analysis of the prognostic and immunological role of ANLN: An onco-immunological biomarker
Authors: Liu Kejun , Cui Lei , Li Cunquan , Tang Chaofeng , Niu Yiming , Hao Ji , Bu Yang , Chen Bendong
Published: August 2022

Anillin actin-binding protein (ANLN) is crucially involved in cell proliferation and migration. Moreover, ANLN is significantly in tumor progression in several types of human malignant tumors; however, it remains unclear whether ANLN acts through common molecular pathways within different tumor microenvironments, pathogeneses, prognoses and immunotherapy contexts. Therefore, this study aimed to perform bioinformatics analysis to examine the correlation of ANLN with tumor immune infiltration, immune evasion, tumor progression, immunotherapy, and tumor prognosis. We observed increased ANLN expression in multiple tumors, which could be involved in tumor cell proliferation, migration, infiltration, and prognosis. The level of ANLN methylation and genetic alteration was associated with prognosis in numerous tumors. ANLN facilitates tumor immune evasion through different mechanisms, which involve T-cell exclusion in different cancer types and tumor-infiltrating immune cells in colon adenocarcinoma, kidney renal clear cell carcinoma, liver hepatocellular carcinoma, and prostate adenocarcinoma. Additionally, ANLN is correlated with immune or chemotherapeutic outcomes in malignant cancers. Notably, ANLN expression may be a predictive biomarker for the response to immune checkpoint inhibitors. Taken together, our findings suggest that ANLN can be used as an onco-immunological biomarker and could serve as a hallmark for tumor screening, prognosis, individualized treatment design, and follow-up.
A systematic analysis of C5ORF46 in gastrointestinal tumors as a potential prognostic and immunological biomarker
Authors: Jiang Yuhong , Wang Xiaobo , Li Lun , He Jun , Jin Qianqian , Long Dongju , Liu Chao , Zhou Weihan , Liu Kuijie
Published: August 2022

Background: Chromosome 5 open reading frame 46 (C5ORF46), also known as antimicrobial peptide with 64 amino acid residues (AP-64) and skin and saliva-secreted protein 1 (SSSP1), belongs to the family of open reading frame genes and encodes a small exosomal protein. C5ORF46 has been implicated in antibacterial activity and associated with patient prognosis in pancreatic cancer, colorectal cancer, and stomach cancer. These findings highlight the importance of C5ORF46 in gastrointestinal (GI) tumor inception and development. However, the prognostic and immunological value of C5ORF46 in human GI tumors remains largely unknown. In this study, we sought to explore the potential value of C5ORF46 in GI tumor prognosis and immunology.

Method: RNA sequencing (RNA-seq) was performed on the tumor and tumor-adjacent normal samples we collected to identify potential target genes for GI tumors. Apart from our RNA-seq data, all original data were downloaded from The Cancer Genome Atlas (TCGA) database and integrated via Strawberry Perl (v 5.32.0) and R (v 4.1.1). The differential expression of C5ORF46 was examined with Oncomine, Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), Cancer Cell Line Encyclopedia (CCLE), the Human Protein Atlas (HPA) and TCGA databases. The c-BioPortal database was used to investigate the genomic alterations of C5ORF46. The effect of C5ORF46 on prognosis and clinical phenotypes was explored via bioinformatics analyses on the TCGA and GEPIA databases. We used the bioinformatics analyses based on the TCGA database to analyze tumor mutational burden (TMB), microsatellite instability (MSI), tumor immune cell infiltration, and the correlations between C5ORF46 expression and several immune-related genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was carried out via the DAVID website and presented as bubble charts using ShengXinRen online tools. Gene set enrichment analysis (GSEA) was performed using R scripts based on data downloaded from the GSEA website. Immunohistochemistry (IHC) was used to validate the expression of C5ORF46 in GI tumors.

Results: The results of our RNA-seq data indicated a critical role for C5ORF46 in colon carcinogenesis. Consistently, we demonstrated that C5ORF46 was highly expressed in tumor tissues compared to normal tissues in human GI tumors. Moreover, a strong correlation was observed between C5ORF46 expression levels and patient prognosis, staging, TMB, MSI, and immune cell infiltration. Further, C5ORF46 presented as an important regulator in the tumor microenvironment (TME) and was active in the regulation of cancer immune functions. C5ORF46 is significantly correlated with genes regulating inflammation and immune responses.

Conclusion:C5ORF46 may serve as a biomarker for GI tumor prognosis and immunology. C5ORF46 could be a novel target for GI tumor immunotherapy.
COVID-19-specific transcriptomic signature detectable in blood across multiple cohorts
Authors: Välikangas Tommi , Junttila Sini , Rytkönen Kalle T. , Kukkonen-Macchi Anu , Suomi Tomi , Elo Laura L.
Published: August 2022

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading across the world despite vast global vaccination efforts. Consequently, many studies have looked for potential human host factors and immune mechanisms associated with the disease. However, most studies have focused on comparing COVID-19 patients to healthy controls, while fewer have elucidated the specific host factors distinguishing COVID-19 from other infections. To discover genes specifically related to COVID-19, we reanalyzed transcriptome data from nine independent cohort studies, covering multiple infections, including COVID-19, influenza, seasonal coronaviruses, and bacterial pneumonia. The identified COVID-19-specific signature consisted of 149 genes, involving many signals previously associated with the disease, such as induction of a strong immunoglobulin response and hemostasis, as well as dysregulation of cell cycle-related processes. Additionally, potential new gene candidates related to COVID-19 were discovered. To facilitate exploration of the signature with respect to disease severity, disease progression, and different cell types, we also offer an online tool for easy visualization of the selected genes across multiple datasets at both bulk and single-cell levels.
A transmembrane protein family gene signature for overall survival prediction in osteosarcoma
Authors: Du Yuehui , Zeng Xiaohui , Yu Weiwei , Xie Wei
Published: August 2022

The transmembrane (TMEM) protein family is constituted by a large number of proteins that span the lipid bilayer. Dysregulation of TMEM protein genes widely occurs and is associated with clinical outcomes of patients with multiple tumors. Nonetheless, the significance of TMEM genes in the prognosis prediction of patients with osteosarcoma remains largely unclear. Here, we comprehensively analyzed TMEM protein family genes in osteosarcoma using public resources and bioinformatics methods. Prognosis-related TMEM protein family genes were identified by the univariate Cox regression analysis and were utilized to construct a signature based on six TMEM protein family genes (TMEM120B, TMEM147, TMEM9B, TMEM8A, TMEM59, and TMEM39B) in osteosarcoma. The prognostic signature stratified patients into high- and low-risk groups, and validation in the internal and external cohorts confirmed the risk stratification ability of the signature. Functional enrichment analyses of differentially expressed genes between high- and low-risk groups connected immunity with the prognostic signature. Moreover, we found that M2 and M0 macrophages were the most abundant infiltrated immune cell types in the immune microenvironment, and samples of the high-risk group showed a decreased proportion of M2 macrophages. Single-sample gene set enrichment analysis revealed that the scores of neutrophils and Treg were markedly lower in the high-risk group than these in the low-risk group in The Cancer Genome Atlas and GSE16091 cohorts. As for the related immune functions, APC co-inhibition and cytolytic activity exhibited fewer active levels in the high-risk group than that in the low-risk group in both cohorts. Of the six TMEM genes, the expression of TMEM9B was lower in the high-risk group than in the low-risk group and was positively associated with the overall survival of osteosarcoma patients. In conclusion, our TMEM protein family gene-based signature is a novel and clinically useful prognostic biomarker for osteosarcoma patients, and TMEM9B might be a potential therapeutic target in osteosarcoma.
GCNCMI: A Graph Convolutional Neural Network Approach for Predicting circRNA-miRNA Interactions
Authors: He Jie , Xiao Pei , Chen Chunyu , Zhu Zeqin , Zhang Jiaxuan , Deng Lei
Published: August 2022

The interactions between circular RNAs (circRNAs) and microRNAs (miRNAs) have been shown to alter gene expression and regulate genes on diseases. Since traditional experimental methods are time-consuming and labor-intensive, most circRNA-miRNA interactions remain largely unknown. Developing computational approaches to large-scale explore the interactions between circRNAs and miRNAs can help bridge this gap. In this paper, we proposed a graph convolutional neural network-based approach named GCNCMI to predict the potential interactions between circRNAs and miRNAs. GCNCMI first mines the potential interactions of adjacent nodes in the graph convolutional neural network and then recursively propagates interaction information on the graph convolutional layers. Finally, it unites the embedded representations generated by each layer to make the final prediction. In the five-fold cross-validation, GCNCMI achieved the highest AUC of 0.9312 and the highest AUPR of 0.9412. In addition, the case studies of two miRNAs, hsa-miR-622 and hsa-miR-149-5p, showed that our model has a good effect on predicting circRNA-miRNA interactions. The code and data are available at https://github.com/csuhjhjhj/GCNCMI.
CRISPR screening identifies T cell-intrinsic regulators of CD3-bispecific antibody responses
Authors: Molony Ryan D. , Funk Theresa , Trabucco Gina , Corcoran Erik , Ruddy David , Varadarajan Malini , Elliot GiNell , Piquet Michelle , Lam Joni , Meyer Matthew J. , Wang Hui Qin , Kurtulus Sema , Lu Haihui
Published: August 2022

CD3-engaging bispecific antibodies (BsAbs) enable the formation of an immune synapse between T cells and tumor cells, resulting in robust target cell killing not dependent on a preexisting tumor specific T cell receptor. While recent studies have shed light on tumor cell-specific factors that modulate BsAb sensitivity, the T cell-intrinsic determinants of BsAb efficacy and response durability are poorly understood. To better clarify the genes that shape BsAb-induced T cell responses, we conducted targeted analyses and a large-scale unbiasedin vitroCRISPR/Cas9-based screen to identify negative regulators of BsAb-induced T cell proliferation. These analyses revealed that CD8+ T cells are dependent on CD4+ T cell-derived signaling factors in order to achieve sustained killingin vitro. Moreover, the mammalian target of rapamycin (mTOR) pathway and several other candidate genes were identified as intrinsic regulators of BsAb-induced T cell proliferation and/or activation, highlighting promising approaches to enhancing the utility of these potent therapeutics.
LNA-anti-miR-150 alleviates renal interstitial fibrosis by reducing pro-inflammatory M1/M2 macrophage polarization
Authors: Hao Xiangnan , Luan Junjun , Jiao Congcong , Ma Cong , Feng Zixuan , Zhu Lingzi , Zhang Yixiao , Fu Jingqi , Lai Enyin , Zhang Beiru , Wang Yanqiu , Kopp Jeffrey B. , Pi Jingbo , Zhou Hua
Published: August 2022

Renal interstitial fibrosis (RIF) is a common pathological feature contributing to chronic injury and maladaptive repair following acute kidney injury. Currently, there is no effective therapy for RIF. We have reported that locked nuclear acid (LNA)-anti-miR-150 antagonizes pro-fibrotic pathways in human renal tubular cells by regulating the suppressor of cytokine signal 1 (SOCS1)/Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. In the present study, we aimed to clarify whether LNA-anti-miR-150 attenuates folic acid-induced RIF mice by regulating this pathway and by reducing pro-inflammatory M1/M2 macrophage polarization. We found that renal miR-150 was upregulated in folic acid-induced RIF mice at day 30 after injection. LNA-anti-miR-150 alleviated the degree of RIF, as shown by periodic acid–Schiff and Masson staining and by the expression of pro-fibrotic proteins, including alpha-smooth muscle actin and fibronectin. In RIF mice, SOCS1 was downregulated, and p-JAK1 and p-STAT1 were upregulated. LNA-anti-miR-150 reversed the changes in renal SOCS1, p-JAK1, and p-STAT1 expression. In addition, renal infiltration of total macrophages, pro-inflammatory M1 and M2 macrophages as well as their secreted cytokines were increased in RIF mice compared to control mice. Importantly, in folic acid-induced RIF mice, LNA-anti-miR-150 attenuated the renal infiltration of total macrophages and pro-inflammatory subsets, including M1 macrophages expressing CD11c and M2 macrophages expressing CD206. We conclude that the anti-renal fibrotic role of LNA-anti-miR-150 in folic acid-induced RIF mice may be mediated by reducing pro-inflammatory M1 and M2 macrophage polarization via the SOCS1/JAK1/STAT1 pathway.
Fibroblasts: Immunomodulatory factors in refractory diabetic wound healing
Authors: Liu Ye , Liu Yiqiu , He Wenjie , Mu Xingrui , Wu Xingqian , Deng Junyu , Nie Xuqiang
Published: August 2022

Diabetes is a systemic disease in which patients with diabetes may develop peripheral neuropathy of the lower extremities and peripheral vascular disease due to long-term continuous exposure to high glucose. Delayed wound healing in diabetes is one of the major complications of diabetes. Slow wound healing in diabetic patients is associated with high glucose toxicity. When the condition deteriorates, the patient needs to be amputated, which seriously affects the quality of life and even endangers the life of the patient. In general, the delayed healing of diabetes wound is due to the lack of chemokines, abnormal inflammatory response, lack of angiogenesis and epithelial formation, and fibroblast dysfunction. The incidence of several chronic debilitating conditions is increasing in patients with diabetes, such as chronic renal insufficiency, heart failure, and hepatic insufficiency. Fibrosis is an inappropriate deposition of extracellular matrix (ECM) proteins. It is common in diabetic patients causing organ dysfunction. The fibrotic mechanism of diabetic fibroblasts may involve direct activation of permanent fibroblasts. It may also involve the degeneration of fibers after hyperglycemia stimulates immune cells, vascular cells, or organ-specific parenchymal cells. Numerous studies confirm that fibroblasts play an essential role in treating diabetes and its complications. The primary function of fibroblasts in wound healing is to construct and reshape the ECM. Nowadays, with the widespread use of single-cell RNA sequencing (scRNA-seq), an increasing number of studies have found that fibroblasts have become the critical immune sentinel cells, which can detect not only the activation and regulation of immune response but also the molecular pattern related to the injury. By exploring the heterogeneity and functional changes of fibroblasts in diabetes, the manuscript discusses that fibroblasts may be used as immunomodulatory factors in refractory diabetic wound healing, providing new ideas for the treatment of refractory diabetic wound healing.