bluuebunny/crossref_metadata_2025 huggingface dataset:
Exosomes as Efficient Nanocarriers in Osteosarcoma: Biological Functions and Potential Clinical Applications
Authors: Yang Lingkai , Huang Xin , Guo Haoyu , Wang Lutong , Yang Wenbo , Wu Wei , Jing Doudou , Shao Zengwu
Published: October 2021

Osteosarcoma is the most common bone tumor affecting both adolescents and children. Although localized osteosarcoma has an overall survival of >70% in the clinic, metastatic, refractory, and recurrent osteosarcoma have poorer survival rates. Exosomes are extracellular vesicles released by cells and originally thought to be a way for cells to discard unwanted products. Currently, exosomes have been reported to be involved in intercellular cross-talk and induce changes in cellular behavior by transferring cargoes (proteins, DNA, RNA, and lipids) between cells. Exosomes regulate osteosarcoma progression, and processes such as tumorigenesis, proliferation, metastasis, angiogenesis, immune evasion, and drug resistance. Increasing evidences shows that exosomes have significant potential in promoting osteosarcoma progression and development. In this review, we describe the current research status of exosomes in osteosarcoma, focusing on the biological functions of osteosarcoma exosomes as well as their application in osteosarcoma as diagnostic biomarkers and therapeutic targets.
Regulatory T Cells Improved the Anti-cirrhosis Activity of Human Amniotic Mesenchymal Stem Cell in the Liver by Regulating the TGF-β-Indoleamine 2,3-Dioxygenase Signaling
Authors: Deng Zhenhua , Zhou Jinren , Mu Xiaoxin , Gu Jian , Li Xiangyu , Shao Qing , Li Jinyang , Yang Chao , Han Guoyong , Zhao Jie , Xia Yongxiang
Published: October 2021

Liver fibrosis is a progression stage of chronic liver disease, while current therapies cannot cure or attune cirrhosis effectively. Human amniotic mesenchymal stromal cell (hAMSC) presented immunoregulatory and tissue repairability of multiple illnesses. Regulatory T cells (Treg) had been proved to be functional in reducing immune cell activity. We showed that co-infusion of hAMSC and Treg prevented mild liver fibrosis comparing with hAMSC or Treg alone group. In vitro study indicated that the addition of Treg or the supernatant of Treg improved the hepatocyte growth factor (HGF) secreting and cell differentiation ability of hAMSC. Reduction of TGF-β significantly decreased the HGF secreting and differentiation of hAMSC. Multiple signal neutralizers were added to the culture to understand further the mechanism, which showed that 1-MT, the suppressor of Indoleamine 2,3-dioxygenase (IDO), was involved in the effect of TGF-β in regulating hAMSC. Depletion of TGF-β or IDO signaling successfully abolished the effect of Treg in improving hAMSC’s function both in vitro and vivo. Finally, our result indicated that Treg improved the function of hAMSC by regulating the TGF-β-IDO signaling and co-infusion of hAMSC and Treg provided a promising approach for treating liver cirrhosis.
Irisin Stimulates the Release of CXCL1 From Differentiating Human Subcutaneous and Deep-Neck Derived Adipocytes via Upregulation of NFκB Pathway
Authors: Shaw Abhirup , Tóth Beáta B. , Király Róbert , Arianti Rini , Csomós István , Póliska Szilárd , Vámos Attila , Korponay-Szabó Ilma R. , Bacso Zsolt , Győry Ferenc , Fésüs László , Kristóf Endre
Published: October 2021

Thermogenic brown and beige adipocytes might open up new strategies in combating obesity. Recent studies in rodents and humans have indicated that these adipocytes release cytokines, termed “batokines”. Irisin was discovered as a polypeptide regulator of beige adipocytes released by myocytes, primarily during exercise. We performed global RNA sequencing on adipocytes derived from human subcutaneous and deep-neck precursors, which were differentiated in the presence or absence of irisin. Irisin did not exert an effect on the expression of characteristic thermogenic genes, while upregulated genes belonging to various cytokine signaling pathways. Out of the several upregulated cytokines,CXCL1, the highest upregulated, was released throughout the entire differentiation period, and predominantly by differentiated adipocytes. Deep-neck area tissue biopsies also showed a significant release of CXCL1 during 24 h irisin treatment. Gene expression data indicated upregulation of the NFκB pathway upon irisin treatment, which was validated by an increase of p50 and decrease of IκBα protein level, respectively. Continuous blocking of the NFκB pathway, using a cell permeable inhibitor of NFκB nuclear translocation, significantly reduced CXCL1 release. The released CXCL1 exerted a positive effect on the adhesion of endothelial cells. Together, our findings demonstrate that irisin stimulates the release of a novel adipokine, CXCL1,viaupregulation of NFκB pathway in neck area derived adipocytes, which might play an important role in improving tissue vascularization.
Portland Versus Alkaline Cement: Continuity or Clean Break: “A Key Decision for Global Sustainability”
Authors: Palomo A. , Maltseva O. , Garcia-Lodeiro I. , Fernández-Jiménez A.
Published: October 2021

This review undertakes rigorous analysis of much of the copious literature available to the scientific community on the use of alkali-activated binders (AABs) in construction. The authors’ main intention is to categorically refute arguments of that part of the scientific community underestimating or even dismissing the actual potential of AABs as alternatives to Portland cement (PC). The main premise invoked in support of those arguments is a presumed lack of material resources for precursors that would make AAB industrial-scale production unfeasible anywhere on the planet (a substantial number of scientific papers show that the raw materials required for AAB manufacture are in abundance worldwide). The review also analyses the role of alkaline activators in the chemistry of AABs; it is important to clarify and highlight that alkaline activators are not, by any means, confined to the two synthetic products (caustic soda and waterglass) mostly employed by researchers; other sustainable and efficient products are widely available. Finally, the review deals with the versatility of AAB production processes. The technologies required for the large scale manufacturing of AABs are mostly already in place in PC factories; actually no huge investment is required to transform a PC plant in a AAB factory; and quality and compositional uniformity of Alkaline Cements (binders produced through an industrial process) would be guaranteed. The last conclusions extracted from this review-paper are related with: i) the low carbon footprint of one-part AABs and ii) the urgent need of exploring standardization formulas allowing the commercial development of (sustainable) binders different from PC.
Genomic Variations in the Structural Proteins of SARS-CoV-2 and Their Deleterious Impact on Pathogenesis: A Comparative Genomics Approach
Authors: Mohammad Taj , Choudhury Arunabh , Habib Insan , Asrani Purva , Mathur Yash , Umair Mohd , Anjum Farah , Shafie Alaa , Yadav Dharmendra Kumar , Hassan Md. Imtaiyaz
Published: October 2021

A continual rise in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection causing coronavirus disease (COVID-19) has become a global threat. The main problem comes when SARS-CoV-2 gets mutated with the rising infection and becomes more lethal for humankind than ever. Mutations in the structural proteins of SARS-CoV-2, i.e., the spike surface glycoprotein (S), envelope (E), membrane (M) and nucleocapsid (N), and replication machinery enzymes, i.e., main protease (Mpro) and RNA-dependent RNA polymerase (RdRp) creating more complexities towards pathogenesis and the available COVID-19 therapeutic strategies. This study analyzes how a minimal variation in these enzymes, especially in S protein at the genomic/proteomic level, affects pathogenesis. The structural variations are discussed in light of the failure of small molecule development in COVID-19 therapeutic strategies. We have performed in-depth sequence- and structure-based analyses of these proteins to get deeper insights into the mechanism of pathogenesis, structure-function relationships, and development of modern therapeutic approaches. Structural and functional consequences of the selected mutations on these proteins and their association with SARS-CoV-2 virulency and human health are discussed in detail in the light of our comparative genomics analysis.
1-MNA Ameliorates High Fat Diet-Induced Heart Injury by Upregulating Nrf2 Expression and Inhibiting NF-κB in vivo and in vitro
Authors: Song Ziguang , Zhong Xiao , Li Mingyang , Gao Pingping , Ning Zhongping , Sun Zhiqi , Song Xiang
Published: October 2021

High levels of free fatty acids (FFA) are closely associated with obesity and the development of cardiovascular diseases. Recently, nicotinamide adenine dinucleotide (NAD) metabolism has emerged as a potential target for several modern diseases including diabetes. Herein, we explored the underlying mechanisms of NAD metabolism associated with the risk of cardiovascular disease. Our study found that nicotinamide N-methyltransferase (NNMT) mRNA levels were significantly increased in the hearts of FFA-bound-albumin-overloaded mice and in H9C2 cells treated with palmitic acid (PA). We studied the mechanisms underlining the anti-inflammatory and anti-oxidant activities of 1-methylnicotinamide (1-MNA), a metabolite of NNMT. We found a significantly higher level of reactive oxygen species, inflammation, apoptosis, and cell hypertrophy in PA-treated H9C2 cells and this effect was inhibited by 1-MNA treatment. in vivo, 1-MNA improved inflammation, apoptosis, and fibrosis damage in mice and this inhibition was associated with inhibited NF-κB activity. In conclusion, our study revealed that 1-MNA may prevent high fatty diet and PA-induced heart injury by regulating Nrf2 and NF-κB pathways.
Evaluation of Endothelial Dysfunction and Inflammatory Vasculopathy After SARS-CoV-2 Infection—A Cross-Sectional Study
Authors: Jud Philipp , Gressenberger Paul , Muster Viktoria , Avian Alexander , Meinitzer Andreas , Strohmaier Heimo , Sourij Harald , Raggam Reinhard B. , Stradner Martin Helmut , Demel Ulrike , Kessler Harald H. , Eller Kathrin , Brodmann Marianne
Published: October 2021

Background: Rising data suggest that COVID-19 affects vascular endothelium while the underlying mechanisms promoting COVID-19-associated endothelial dysfunction and inflammatory vasculopathy are largely unknown. The aim was to evaluate the contribution of COVID-19 to persisting vascular injury and to identify parameters linked to COVID-19-associated endothelial dysfunction and inflammatory vasculopathy.

Methods: In a cross-sectional design, flow-mediated dilation (FMD), nitroglycerine-related dilation (NMD), pulse-wave velocity (PWV), augmentation index, intima-media thickness (IMT), compounds of the arginine and kynurenine metabolism, homocysteine, von Willebrand factor (vWF), endothelial microparticles (EMP), antiendothelial cell antibodies, inflammatory, and immunological parameters, as well as nailfold capillary morphology were measured in post-COVID-19 patients, patients with atherosclerotic cardiovascular diseases (ASCVD) and healthy controls without prior or recent SARS-CoV-2 infection.

Results: Post-COVID-19 patients had higher values of PWV, augmentation index, IMT, asymmetric and symmetric dimethylarginine, vWF, homocysteine, CD31+/CD42b– EMP, C-reactive protein, erythrocyte sedimentation rate, interleukin-6, and β-2-glycoprotein antibodies as well as lower levels of homoarginine and tryptophan compared to healthy controls (all with p < 0.05). A higher total number of pathologically altered inflammatory conditions and higher rates of capillary ramifications, loss, caliber variability, elongations and bushy capillaries with an overall higher microangiopathy evolution score were also observed in post-COVID-19 patients (all with p < 0.05). Most parameters of endothelial dysfunction and inflammation were comparably altered in post-COVID-19 patients and patients with ASCVD, including FMD and NMD.

Conclusion: COVID-19 may affect arterial stiffness, capillary morphology, EMP and selected parameters of arginine, kynurenine and homocysteine metabolism as well as of inflammation contributing to COVID-19-associated endothelial dysfunction and inflammatory vasculopathy.
Increased Phospholipid Transfer Protein Activity Is Associated With Markers of Enhanced Lipopolysaccharide Clearance in Human During Cardiopulmonary Bypass
Authors: Nguyen Maxime , Gautier Thomas , Reocreux Guillaume , Pallot Gaëtan , Maquart Guillaume , Bahr Pierre-Alain , Tavernier Annabelle , Grober Jacques , Masson David , Bouhemad Belaid , Guinot Pierre-Grégoire
Published: October 2021

Introduction: Lipopolysaccharide (LPS) is a component of gram-negative bacteria, known for its ability to trigger inflammation. The main pathway of LPS clearance is the reverse lipopolysaccharide transport (RLT), with phospholipid transfer protein (PLTP) and lipoproteins playing central roles in this process in experimental animal models. To date, the relevance of this pathway has never been studied in humans. Cardiac surgery with cardiopulmonary bypass is known to favor LPS digestive translocation. Our objective was to determine whether pre-operative PLTP activity and triglyceride or cholesterol-rich lipoprotein concentrations were associated to LPS concentrations in patients undergoing cardiac surgery with cardiopulmonary bypass.

Methods: A post-hoc analysis was conducted on plasma samples obtained from patients recruited in a randomized controlled trial.Total cholesterol, high density lipoprotein cholesterol (HDLc), low density lipoprotein cholesterol (LDLc), triglyceride and PLTP activity were measured before surgery. LPS concentration was measured by mass spectrometry before surgery, at the end of cardiopulmonary bypass and 24 h after admission to the intensive care unit.

Results: High PLTP activity was associated with lower LPS concentration but not with inflammation nor post-operative complications. HDLc, LDLc and total cholesterol were not associated with LPS concentration but were lower in patients developing post-operative adverse events. HDLc was negatively associated with inflammation biomarkers (CRP, PCT). Triglyceride concentrations were positively correlated with LPS concentration, PCT and were higher in patients with post-operative complications.

Conclusion: Our study supports the role of PLTP in LPS elimination and the relevance of RLT in human. PLTP activity, and not cholesterol rich lipoproteins pool size seemed to be the limiting factor for RLT. PLTP activity was not directly related to post-operative inflammation and adverse events, suggesting that LPS clearance is not the main driver of inflammation in our patients. However, HDLc was associated with lower inflammation and was associated with favorable outcomes, suggesting that HDL beneficial anti-inflammatory effects could be, at least in part independent of LPS clearance.
Flume Tests to Investigate the Initiation Mechanism of Loess Mudflows on the Chinese Loess Plateau
Authors: Ma Penghui , Zhuang Jianqi , Zhu Xinghua , Cheng Yuxiang , Liu Cong
Published: October 2021

Loess has a strong water sensitivity, so loess landslides often transform into loess mudflows when water is added on the Chinese Loess Plateau, which results in high casualties and property loss of the Chinese government. In this study, a series of flume tests were designed to study the initiation of loess mudflows. The results reveal that the initiation modes of loess mudflows include large-scale mudflow and retrogressive toe sliding (Type A), and small-scale mudflow and retrogressive toe sliding (Type B). A model was used to analyze the test results that describe the effects of water flow on the potential for hillslope failure and liquefaction. It was found that the soil accumulation was unconditionally stable before a loess mudflow was formed, but as the rainfall continued, the water gradually infiltrated the soil, and the soil accumulation changed from unconditionally stable to unconditionally unstable. Thus, this led to different initiation modes during the tests. For Type A, the water preferentially infiltrated into the area with an uneven density and a large amount of water accumulated. The pore water pressure increased quickly and could not dissipate in time, so the loess liquefied. As the liquefaction area continued to expand and became larger, Type A occurred. Relatively speaking, Type B occurs in soil accumulations with relatively uniform densities. These results provide a certain scientific reference for the study of loess mudflows.
Inflation-Deflation Episodes in the Hengill and Hrómundartindur Volcanic Complexes, SW Iceland
Authors: Ducrocq Cécile , Geirsson Halldór , Árnadóttir Thóra , Juncu Daniel , Drouin Vincent , Gunnarsson Gunnar , Kristjánsson Bjarni R. , Sigmundsson Freysteinn , Hreinsdóttir Sigrún , Tómasdóttir Sigrún , Blanck Hanna
Published: October 2021

Non-eruptive uplift and subsidence episodes remain a challenge for monitoring and hazard assessments in active volcanic systems worldwide. Sources of such deformation may relate to processes such as magma inflow and outflow, motion and phase changes of hydrothermal fluids or magma volatiles, heat transfer from magmatic bodies and heat-mining from geothermal extraction. The Hengill area, in southwest Iceland, hosts two active volcanic systems, Hengill and Hrómundartindur, and two high-temperature geothermal power plants, Hellisheiði and Nesjavellir. Using a combination of geodetic data sets (GNSS and InSAR; Global Navigation Satellite Systems and Interferometry Synthetic Aperture Radar, respectively) and a non-linear inversion scheme to estimate the optimal analytical model parameters, we investigate the ground deformation between 2017–2018. Due to other ongoing deformation processes in the area, such as plate motion, subsidence in the two geothermal production fields, and deep-seated source of contraction since 2006, we estimate 2017–2018 difference velocities by subtracting background deformation, determined from data spanning 2015–2017 (InSAR) or 2009–2017 (GNSS). This method highlights changes in ground deformation observed in 2017–2018 compared to prior years: uplift signal of ∼10 km diameter located in the eastern part of the Hengill area, and geothermal production-related temporal changes in deformation near Húsmúli, in the western part of the Hengill area. We find an inflation source located between the Hengill and Hrómundartindur volcanic complexes, lasting for ∼5 months, with a maximum uplift of ∼12 mm. Our model inversions give a source at depth of ∼6–7 km, located approximately in the same crustal volume as an inferred contracting source in 2006–2017, within the local brittle-ductile transition zone. No significant changes were observed in local seismicity, borehole temperatures and pressures during the uplift episode. These transient inflation and deflation sources are located ∼3 km NW from a source of non-eruptive uplift in the area (1993–1999). We consider possible magmatic and hydrothermal processes as the causes for these inflation-deflation episodes and conclude that further geophysical and geological studies are needed to better understand such episodes.
Genesis of High-Mg Adakites in the Southeastern Margin of North China Craton: Geochemical and U-Pb Geochronological Perspectives
Authors: Zheng Shuo , An Yanfei , Lai Chunkit , Wang Hongzhi , Li Yunfeng
Published: October 2021

In the eastern North China Craton (NCC), Mesozoic tectonics was dominated by the Paleo-Pacific subduction rollback and the Tanlu crustal-scale fault movement. The regional transtension had generated extensive adakitic magmatism, some Cu-Au ore-forming but others not. To establish the geodynamic setting and any metallogenic link for the adakites from the southeastern NCC margin, we analyzed the ore-barren adakitic rocks from underground mines in the Huaibei-Linhuan coalfield (where surface igneous outcrops are scarce), and compared their ages and geochemistry with other mineralized and ore-barren adakites across Eastern China. Zircon U-Pb dating reveals two magmatic episodes in the Huaibei-Linhuan coalfield: 1) early-Early Cretaceous (ca. 130–129 Ma) (quartz-)diorite and granodiorite, and 2) late-Early Cretaceous (ca. 115.8 and 105.8 Ma) microgabbro and dolerite. Whole-rock geochemistry indicates that the (quartz-)diorite and granodiorite are high-Mg adakitic, featured by low K2O/Na2O (avg. 0.33), high Sr/La (avg. 44.3), and lack of correlation between SiO2 (fractionation index) and Sr/Y (avg. 56.55) and MREE/HREE (avg. 1.09), resembling typical adakites derived from oceanic-slab partial melting. Geochronological correlation with the regional tectonic events suggests that the slab-melting may have been caused by the Paleo-Pacific subduction rollback. Further extension and crustal thinning in the late-Early Cretaceous along the southern Tanlu fault may have formed the gabbro-dolerite in the coalfield. Geochemical comparison suggests that parental magma of the Huaibei-Linhuan adakites may have had similar water content [similar zircon 10,000*(Eu/Eu*)/Y and Eu/Eu* ratios] to typical porphyry Cu-Au ore-forming magmas, yet the former may have been considerably more reduced (lower zircon Ce/Nd and whole-rock V/Sc ratios). We considered that the assimilation of Carboniferous-Permian coal seams in the area may have further lowered the magma fO2 and thus its potential to form Cu-Au mineralization.
Pore Connectivity Characterization Using Coupled Wood’s Metal Intrusion and High-Resolution Imaging: A Case of the Silurian Longmaxi Shales From the Sichuan Basin, China
Authors: Yu Lingjie , Liu Keyu , Fan Ming , Pan Zhejun
Published: October 2021

Pore connectivity is crucial for shale gas production. However, the three-dimensional (3D) characteristics and distribution of pore networks and, more fundamentally, the underlying role of different pore types on pore connectivity in shales are inadequately understood. By comparing the 3D pore connectivity derived from direct microstructural imaging of pores filled with Wood’s metal at a pressure corresponding to the finest accessible pore throat in the resolution ranges that may be achieved by X-ray micro-CT and SEM, it is possible to evaluate pore connectivity of different types of shales. The pore connectivity of three shales including a mixed mudstone, siliceous shale, and argillaceous shale from the Silurian Longmaxi Formations is investigated via combined broad ion beam (BIB) polishing, and SEM and X-ray micro-CT imaging after Wood’s metal injection at a pressure up to 380 MPa. The three shales show significant differences in pore connectivity. The mixed mudstone shows excellent pore connectivity in the matrix; the siliceous shale shows an overall poor connectivity with only a small amount of OM (organic matter) pores immediately adjacent to microfractures displaying interconnectivity, while the pores in the argillaceous shale, dominated by plate-like clay pores, are largely not interconnected.
Minimum Detectable Mass and Volume Fluxes During Magmatic Recharge at High Prominence Volcanoes: An Application to Erciyes Dağ Volcano (Turkey)
Authors: Males Katie , Gottsmann Jo
Published: October 2021

Magma reservoir recharge is widely recognised as a precursor of eruptive activity. However, the causative relationships between reservoir rejuvenation and surface observables such as gravitational potential field changes and ground deformation are still poorly understood. At intermediate and silicic intra-plate volcanoes where crustal mechanical heterogeneity combined with high-prominence are expected to fundamentally affect the crustal stress and strain relationship, protracted period of repose and absence of monitoring data raise questions about the detectability of magma recharge. Here we report results from integrated geodetic forward modelling of ground displacements and gravity changes from reservoir recharge at Erciyes Dağ, a large prominence (∼2,800 m), yet poorly studied, stratovolcano of the Central Anatolian Volcanic Province in Turkey. The most recent eruption at ∼7000 BC, close proximity to the Kayseri Metropolitan Area and absence of dedicated volcano monitoring set a precedent to explore stealth magmatic processes at the volcano. Using finite element analysis we systematically explore the influence of subsurface mechanical heterogeneities and topography on surface deformation and gravity changes from magmatic recharge of Erciyes Dağ’s reservoir. We show that whilst crustal heterogeneity amplifies ground displacements and gravity variations, the volcano’s substantial prominence has the opposite effect. For generic reservoir pressure and density changes of 10 MPa and 10 kg m−3 predicted vertical displacements vary by a factor of 5 while residual gravity changes vary by a factor of 12 between models ignoring topography or mechanical heterogeneity and those that do not. We deduce reservoir volume and mass changes of order 10–3 km3 and 1010 kg, respectively, at the detectability limit of conventional surveying techniques at the volcano. Though dependent on model assumptions, all results indicate that magma recharge at Erciyes Dağ may go undetected at fluxes 1) sufficient to maintain an active reservoir containing eruptable magma and 2) similar to those reported for intermediate/silicic volcanoes with repose times of 100–1,000s of years (e.g., Parinacota) and persistently active mafic volcanoes such as Mt. Etna and Stromboli. Our findings may be utilised to inform integrated geodetic and gravimetric monitoring at Erciyes Dağ and other large prominence silicic volcanoes and could provide early insights into reservoir rejuvenation with implications for the development of disaster risk reduction initiatives.
Change of East-Asian Summer Precipitation Associated With Strong El Niño Under the Future Emission Scenarios
Authors: Huang Yu , Ren Hong-Li , Liu Minghong
Published: October 2021

Strong Eastern-Pacific type El Niño (EP-El Niño) events have significant impacts on the decaying-summer precipitation over East Asia (EA). It has been demonstrated that frequency of strong EP-El Niños will increase and associated precipitation will become more severe and complex under future high emission scenarios. In this study, using simulations of CMIP5 and CMIP6, changes of the summer precipitation pattern related to strong EP-El Niño during its decay phase and the possible mechanism as responding to high emission scenarios are examined. Precipitation anomaly patterns over EA of strong EP events show a large inter-model spread in historical simulations between the CMIP models where CMIP6 is not superior to CMIP5. Under high emission scenarios, changes of summer precipitation anomalies related to strong EP events tend to increase over the southern EA and decrease around the northern EA from CMIP5, while there is an overall increase in the whole EA from CMIP6. The common change is featured by the increase of precipitation over southeastern China under high emission scenarios. This could be mainly attributed to the anticyclonic circulation from the South China Sea to the western North Pacific as a delayed response to more frequent strong EP-El Niños, which favors an increase in water vapor fluxes converging into the southeastern China.
Quantitative Acetylomics Revealed Acetylation-Mediated Molecular Pathway Network Changes in Human Nonfunctional Pituitary Neuroendocrine Tumors
Authors: Wen Siqi , Li Jiajia , Yang Jingru , Li Biao , Li Na , Zhan Xianquan
Published: October 2021

Acetylation at lysine residue in a protein mediates multiple cellular biological processes, including tumorigenesis. This study aimed to investigate the acetylated protein profile alterations and acetylation-mediated molecular pathway changes in human nonfunctional pituitary neuroendocrine tumors (NF-PitNETs). The anti-acetyl antibody-based label-free quantitative proteomics was used to analyze the acetylomes between NF-PitNETs (n = 4) and control pituitaries (n = 4). A total of 296 acetylated proteins with 517 acetylation sites was identified, and the majority of which were significantly down-acetylated in NF-PitNETs (p<0.05 or only be quantified in NF-PitNETs/controls). These acetylated proteins widely functioned in cellular biological processes and signaling pathways, including metabolism, translation, cell adhesion, and oxidative stress. The randomly selected acetylated phosphoglycerate kinase 1 (PGK1), which is involved in glycolysis and amino acid biosynthesis, was further confirmed with immunoprecipitation and western blot in NF-PitNETs and control pituitaries. Among these acetylated proteins, 15 lysine residues within 14 proteins were down-acetylated and simultaneously up-ubiquitinated in NF-PitNETs to demonstrate a direct competition relationship between acetylation and ubiquitination. Moreover, the potential effect of protein acetylation alterations on NF-PitNETs invasiveness was investigated. Overlapping analysis between acetylomics data in NF-PitNETs and transcriptomics data in invasive NF-PitNETs identified 26 overlapped molecules. These overlapped molecules were mainly involved in metabolism-associated pathways, which means that acetylation-mediated metabolic reprogramming might be the molecular mechanism to affect NF-PitNET invasiveness. This study provided the first acetylomic profiling and acetylation-mediated molecular pathways in human NF-PitNETs, and offered new clues to elucidate the biological functions of protein acetylation in NF-PitNETs and discover novel biomarkers for early diagnosis and targeted therapy of NF-PitNETs.
5G Wireless Networks in the Future Renewable Energy Systems
Authors: Strielkowski Wadim , Dvořák Marek , Rovný Patrik , Tarkhanova Elena , Baburina Natalia
Published: October 2021

This paper focuses on the strategies that employ the fifth generation (5G) wireless networks in the optimal management of demand-side response in the future energy systems with the high penetration of renewable energy sources (RES). It also provides a comparison between advantages and challenges of 5G networks in demand-response renewable energy grids. Large-scale renewable energy integration always leads to a mismatch between generation and load demand in the short run due to the intermittency. It is often envisioned that 5G wireless networks that were recently launched and would most likely be fully deployed worldwide by 2035 would bring many technological and economic benefits for a plethora of the future high-renewables grids featuring electric transport and heating as well as prosumers generating renewable energy and trading it back to the grid (for example, in the vehicle-to-grid (V2G) framework) and among themselves using peer-to-peer (P2P) networks. Our paper offers a comprehensive analysis of 5G architecture with the perspectives of optimal management of demand-side response in the smart grids of the future. We show that the effective deployment of faster and more reliable wireless networks would allow faster data transfers and processing, including peer-to-peer (P2P) energy trade market, Internet of Vehicles (IoV) market, or faster smart metering, and thence open the path for the full-fledged Internet of Energy (IoE). Moreover, we show that 5G wireless networks might become in the future sustainable energy systems paving the road to even more advanced technologies and the new generations of networks. In addition, we demonstrate that for the effective management of energy demand-side response with a high share of renewables, certain forms of governments funding and incentives might be needed. These are required to strengthen the support of RES and helping to shift to the green economy.
Overview of Oman Power Transmission System and Protection Schemes for Effective Energy Management in Smart Grid Operations
Authors: Al Omairi Saif , Al Balushi Marya , Okedu Kenneth E.
Published: October 2021

This article presents an overview of the transmission system and protection schemes employed in the national power grid of Oman. The technical design requirements considering the percentage of allowable limits for the different transmission voltage levels in the power grid of Oman were considered based on the electrical standards and grid codes of Oman. Also, the protection and fault requirements based on relay settings and backup protection were some of the factors considered in this study. More so, the power flow, peak, and off-peak voltage profiles of the main interconnection and Dhofar transmission systems were analyzed in detail, considering projections for 2021 and 2025, respectively, for effective energy management and smart grid operations. The current protection equipment of the power grid of Oman was evaluated, and some improvement schemes were proposed considering the implementation of the new technology for smart grid operation. The continuous investment in the transmission system of the Oman power grid and the use of updated protection technology would lead to the enhancement of the performance of the Oman transmission system to reach a high-level power transmission availability.
Analysis of the Fee-to-Tax Reform on Water Resources in China
Authors: Chen Zi-Rui , Yuan Yuan , Xiao Xu
Published: October 2021

The Resource Tax Law was officially implemented on September 1, 2020, in China. This law presents the “Fee-to-Tax” reform of water resources. This article compares the effects of the “Fee-to-Tax” reform under asymmetric duopoly conditions with perfect information. The mechanisms of the two policies are different when all firms simultaneously respond to water resources: the water resource fee affects output by reducing market size, while the water resource tax reduces output by amplifying the weighted cost difference effects between companies. Water resource taxes work better than fees for eliminating backward production capacity. A comparison of the situation when companies respond sequentially is also carried out. When a low-cost firm is in the leading position, the collection of fees actually reduces the output difference, whereas the tax improves it. When a high-cost firm acts as a leader, the effects depend on the cost difference. When the cost difference between firms is small, the first-move advantage of high-cost firms dominates the cost advantages of low-cost firms. Therefore, a higher tax rate yields a smaller output difference. When cost differences are relatively larger, the cost advantage of low-cost firms dominates the first-move advantage of high-cost firms. As the operational cost for reducing water consumption increases, the reduced water consumption first increases and then decreases.
Tackling Data Quality When Using Low-Cost Air Quality Sensors in Citizen Science Projects
Authors: Watne Ågot K. , Linden Jenny , Willhelmsson Jens , Fridén Håkan , Gustafsson Malin , Castell Nuria
Published: October 2021

Using low-cost air quality sensors (LCS) in citizen science projects opens many possibilities. LCS can provide an opportunity for the citizens to collect and contribute with their own air quality data. However, low data quality is often an issue when using LCS and with it a risk of unrealistic expectations of a higher degree of empowerment than what is possible. If the data quality and intended use of the data is not harmonized, conclusions may be drawn on the wrong basis and data can be rendered unusable. Ensuring high data quality is demanding in terms of labor and resources. The expertise, sensor performance assessment, post-processing, as well as the general workload required will depend strongly on the purpose and intended use of the air quality data. It is therefore a balancing act to ensure that the data quality is high enough for the specific purpose, while minimizing the validation effort. The aim of this perspective paper is to increase awareness of data quality issues and provide strategies to minimizing labor intensity and expenses while maintaining adequate QA/QC for robust applications of LCS in citizen science projects. We believe that air quality measurements performed by citizens can be better utilized with increased awareness about data quality and measurement requirements, in combination with improved metadata collection. Well-documented metadata can not only increase the value and usefulness for the actors collecting the data, but it also the foundation for assessment of potential integration of the data collected by citizens in a broader perspective.
Effects of Forestry on Carbon Emissions in China: Evidence From a Dynamic Spatial Durbin Model
Authors: Li Zaijun , Mighri Zouheir , Sarwar Suleman , Wei Chen
Published: October 2021

Research has proved the significance of forests in controlling carbon emissions, however, our research sheds light on the management of existing forests to combat climate change. To examine the role of forestation and forest investment activities, dynamic spatial techniques are used for 30 provinces of China. The results suggest that forest investment and management not only reduce carbon locally but also in neighboring provinces. Furthermore, the findings of the current study confirmed that forest investment is the most viable practice to control carbon emissions in China instead of just increasing total forest area. Reforms regarding the management of forests would be a good policy for both pollution reduction and employment generation.
The Impact of Quality of Governance, Renewable Energy and Foreign Direct Investment on Sustainable Development in Cee Countries
Authors: Simionescu Mihaela , Szeles Monica Răileanu , Gavurova Beata , Mentel Urszula
Published: October 2021

Recent debates on the Environmental Kuznets Curve (EKC) in the context of the European Green Deal highlights that pollution could be controlled using channels other than economic development. The role of renewable energy consumption in reducing pollution should be correlated with quality of governance, which could support initiatives for a cleaner environment. This study considers the renewable Kuznets curve for 10 Central and Eastern European countries in the period 2006–2019, using economic indicators (index of economic freedom, foreign direct investment, domestic credit to private sector and labour productivity) as control variables and indicators reflecting the quality of governance (Worldwide Governance Indicators and Google Trend indexes associated to key-word corruption in each language). The research is based on two types of panel data models: panel dynamic OLS model (PDOLS) and panel autoregressive distributed lag models based on pooled mean group (PMG) estimator. The results indicate that government effectiveness reduces pollution in both the short-run and long-run, while control of corruption and rule of law supports environmental protection in the long-run. Google searches for corruption as a proxy for quality of governance indicate that tGHG emissions have immediate and practical implications in nowcasting pollution.
Exome-Wide Association Study Identifies East Asian-Specific Missense Variant MTHFR C136T Influencing Homocysteine Levels in Chinese Populations RH: ExWAS of tHCY in a Chinese Population
Authors: Liu Tianzi , Momin Mohetaboer , Zhou Huiyue , Zheng Qiwen , Fan Fangfang , Jia Jia , Liu Mengyuan , Bao Minghui , Li Jianping , Huo Yong , Liu Jialin , Zhang Yaning , Mao Xuemei , Han Xiao , Hu Zhiyuan , Zeng Changqing , Liu Fan , Zhang Yan
Published: October 2021

Plasma total homocysteine (tHCY) is a known risk factor of a wide range of complex diseases. No genome scans for tHCY have been conducted in East Asian populations. Here, we conducted an exome-wide association study (ExWAS) for tHCY in 5,175 individuals of Chinese Han origin, followed by a replication study in 668 Chinese individuals. The ExWAS identified two loci, 1p36.22 (lead single-nucleotide polymorphism (SNP) rs1801133, MTHFR C677T) and 16q24.3 (rs1126464, DPEP1), showing exome-wide significant association with tHCY (p < 5E−7); and both loci have been previously associated with tHCY in non-East Asian populations. Both SNPs were replicated in the replication study (p < 0.05). Conditioning on the genotype of C677T and rs1126464, we identified a novel East Asian-specific missense variant rs138189536 (C136T) of MTHFR (p = 6.53E−10), which was also significant in the replication study (p = 9.8E−3). The C136T and C677T variants affect tHCY in a compound heterozygote manner, where compound heterozygote and homozygote genotype carriers had on average 43.4% increased tHCY than had other genotypes. The frequency of the homozygote C677T genotype showed an inverse-U-shaped geospatial pattern globally with a pronounced frequency in northern China, which coincided with the high prevalence of hyperhomocysteinemia (HHCY) in northern China. A logistic regression model of HHCY status considering sex, age, and the genotypes of the three identified variants reached an area under the receiver operating characteristic curve (AUC) value of 0.74 in an independent validation cohort. These genetic observations provide new insights into the presence of multiple causal mutations at the MTHFR locus, highlight the role of genetics in HHCY epidemiology among different populations, and provide candidate loci for future functional studies.
A Novel Autophagy-Related Marker for Improved Differential Diagnosis of Rheumatoid Arthritis and Osteoarthritis
Authors: Huang Rong-zhi , Zheng Jie , Liu Feng-ling , Li Qing-ling , Huang Wen-hui , Zhang Dan-meng , Wu Qiang-chu
Published: October 2021

Rheumatoid arthritis (RA) and osteoarthritis (OA) are two most common rheumatic diseases in the world. Although there are standard methods for the diagnosis of both RA and OA, the differentials in some cases are poor. With deepening research, the role of autophagy in maintaining cell homeostasis and thus enabling cells adapt to external environments has become increasingly prominent. Both RA and OA, two diseases with inherent differences in pathogenesis, gradually show differences in autophagy levels. Our study therefore aims to further understand differences in pathogenesis of RA and OA through in-depth studies of autophagy in RA and OA. We also define appropriate autophagy-related markers as recognition indicators. Differences in autophagy levels between RA and OA were found based on analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and single-sample gene set enrichment (ssGSEA). These differences were mainly caused by 134 differentially expressed genes (DEGs). In two autophagy-related genes, CXCR4 and SERPINA1, there existed significant statistical difference between RA and OA. An autophagy related index (ARI) was thus successfully constructed based on CXCR4 and SERPINA by binary logistic regression of the generalized linear regression (GLR) algorithm. Pearson analysis indicated that the expression of CXCR4, SERPINA1, and ARI were closely correlated with autophagy scores and immune infiltration. Moreover, ARI showed high disease identification through receiver operating characteristic (ROC) analysis (AUCtesting cohort = 0.956, AUCtraining cohort = 0.867). These results were then verified in GSE12021 independent cohort. In conclusion, ARI associated with autophagy and immune infiltration was successfully constructed for accurately identifying OA and RA. The index, thus, has great potential in clinical applications.
Population Genetic Polymorphism of Skeletal Muscle Strength Related Genes in Five Ethnic Minorities in North China
Authors: Dong Bonan , Li Qiuyan , Zhang Tingting , Liang Xiao , Jia Mansha , Fu Yansong , Bai Jing , Fu Songbin
Published: October 2021

Musculoskeletal performance is a complex trait influenced by environmental and genetic factors, and it has different manifestations in different populations. Heilongjiang province, located in northern China, is a multi-ethnic region with human cultures dating back to the Paleolithic Age. The Daur, Hezhen, Ewenki, Mongolian and Manchu ethnic groups in Heilongjiang province may have strong physical fitness to a certain extent. Based on the genetic characteristics of significant correlation between some important genes and skeletal muscle function, this study selected 23 SNPs of skeletal muscle strength-related genes and analyzed the distribution of these loci and genetic diversity in the five ethnic groups. Use Haploview (version 4.1) software to calculate the chi-square and the Hardy-Weinberg equilibrium to assess the difference between the two ethnic groups. Use R (version 4.0.2) software to perform principal component analysis of different ethnic groups. Use MEGA (version 7.0) software to construct the phylogenetic tree of different ethnic groups. Use POPGENE (version 1.32) software to calculate the heterozygosity and the FST values of 23 SNPs. Use Arlequin (version 3.5.2.2) software to analyze molecular variance (AMOVA) among 31 populations. The results showed that there was haplotype diversity of VDR, angiotensin-converting enzyme, ACTN3, EPO and IGF1 genes in the five ethnic groups, and there were genetic differences in the distribution of these genes in the five ethnic groups. Among them, the average gene heterozygosity (AVE_HET) of the 23 SNPs in the five populations was 0.398. The FST values of the 23 SNPs among the five ethnic groups varied from 0.0011 to 0.0137. According to the principal component analysis, the genetic distance of Daur, Mongolian and Ewenki is relatively close. According to the phylogenetic tree, the five ethnic groups are clustered together with the Asian population. These data will enrich existing genetic information of ethnic minorities.
Rapid Identification of the Tumor-Specific Reactive TIL Repertoire via Combined Detection of CD137, TNF, and IFNγ, Following Recognition of Autologous Tumor-Antigens
Authors: Draghi Arianna , Chamberlain Christopher Aled , Khan Shawez , Papp Krisztian , Lauss Martin , Soraggi Samuele , Radic Haja Dominike , Presti Mario , Harbst Katja , Gokuldass Aishwarya , Kverneland Anders , Nielsen Morten , Westergaard Marie Christine Wulff , Andersen Mads Hald , Csabai Istvan , Jönsson Göran , Szallasi Zoltan , Svane Inge Marie , Donia Marco
Published: October 2021

Detecting the entire repertoire of tumor-specific reactive tumor-infiltrating lymphocytes (TILs) is essential for investigating their immunological functions in the tumor microenvironment. Current in vitro assays identifying tumor-specific functional activation measure the upregulation of surface molecules, de novo production of antitumor cytokines, or mobilization of cytotoxic granules following recognition of tumor-antigens, yet there is no widely adopted standard method. Here we established an enhanced, yet simple, method for identifying simultaneously CD8+ and CD4+ tumor-specific reactive TILs in vitro, using a combination of widely known and available flow cytometry assays. By combining the detection of intracellular CD137 and de novo production of TNF and IFNγ after recognition of naturally-presented tumor antigens, we demonstrate that a larger fraction of tumor-specific and reactive CD8+ TILs can be detected in vitro compared to commonly used assays. This assay revealed multiple polyfunctionality-based clusters of both CD4+ and CD8+ tumor-specific reactive TILs. In situ, the combined detection of TNFRSF9, TNF, and IFNG identified most of the tumor-specific reactive TIL repertoire. In conclusion, we describe a straightforward method for efficient identification of the tumor-specific reactive TIL repertoire in vitro, which can be rapidly adopted in most cancer immunology laboratories.