bluuebunny/crossref_metadata_2025 huggingface dataset:
Current Perspectives on Achieving Pronounced Enteric Methane Mitigation From Ruminant Production
Authors: Ungerfeld Emilio M. , Beauchemin Karen A. , Muñoz Camila
Published: January 2022

Limiting global warming to 1.5°C above pre-industrial levels by 2050 requires achieving net zero emissions of greenhouse gases by 2050 and a strong decrease in methane (CH4) emissions. Our aim was to connect the global need for mitigation of the emissions of greenhouse gases and enteric CH4 from ruminant production to basic research on the biological consequences of inhibiting rumen methanogenesis in order to better design strategies for pronounced mitigation of enteric CH4 production without negative impacts on animal productivity or economic returns. Ruminant production worldwide has the challenge of decreasing its emissions of greenhouse gases while increasing the production of meat and milk to meet consumers demand. Production intensification decreases the emissions of greenhouse gases per unit of product, and in some instances has decreased total emissions, but in other instances has resulted in increased total emissions of greenhouse gases. We propose that decreasing total emission of greenhouse gases from ruminants in the next decades while simultaneously increasing meat and milk production will require strong inhibition of rumen methanogenesis. An aggressive approach to pronounced inhibition of enteric CH4 emissions is technically possible through the use of chemical compounds and/or bromoform-containing algae, but aspects such as safety, availability, government approval, consumer acceptance, and impacts on productivity and economic returns must be satisfactorily addressed. Feeding these additives will increase the cost of ruminant diets, which can discourage their adoption. On the other hand, inhibiting rumen methanogenesis potentially saves energy for the host animal and causes profound changes in rumen fermentation and post-absorptive metabolism. Understanding the biological consequences of methanogenesis inhibition could allow designing strategies to optimize the intervention. We conducted meta-regressions using published studies with at least one treatment with >50% inhibition of CH4 production to elucidate the responses of key rumen metabolites and animal variables to methanogenesis inhibition, and understand possible consequences on post-absorptive metabolism. We propose possible avenues, attainable through the understanding of biological consequences of the methanogenesis inhibition intervention, to increase animal productivity or decrease feed costs when inhibiting methanogenesis.
lncRNA/miR-29c-Mediated High Expression of LOX Can Influence the Immune Status and Chemosensitivity and Can Forecast the Poor Prognosis of Gastric Cancer
Authors: Nai Aitao , Zeng Huihui , Wu Qiong , He Zirui , Zeng Shuwen , Bashir Shoaib , Ma Feng , He Jie , Wan Wei , Xu Meng
Published: January 2022

Gastric carcinoma is the fourth most prevalent cause of cancer-related deaths worldwide because of dismal prognosis and few therapeutic options. Accumulated studies have indicated that targeting lysyl oxidase (LOX) family members may serve as an anticancer strategy. Nevertheless, the specific mechanisms of LOX in stomach carcinoma are still unclear. In this study, we demonstrated that LOX is significantly different in 13 types of cancers and may act as a potential therapeutic target, especially in stomach carcinoma. Moreover, overexpression of LOX in gastric carcinoma was validated by multiple databases and contributed to the poor overall survival (OS), progression-free survival (PFS) and post-progression survival (PPS) of stomach adenocarcinoma (STAD) patients. Next, based on the ceRNA hypothesis, the HIF1A-AS2/RP11-366L20.2-miR-29c axis was characterized as the upstream regulatory mechanism of LOX gene overexpression in gastric cancer by combining correlation analysis, expression analysis, and survival analysis. Finally, we illustrated that LOX gene overexpression leads to dismal prognosis of gastric cancer, perhaps through promoting M2 macrophage polarization and tumor immune escape and enhancing drug resistance of tumor cells to chemotherapeutic drugs. Our research demonstrate that LOX may be potentially applied as a novel prognostic marker and targeting inhibition of LOX holds promise as a treatment strategy for gastric cancer.
Hindlimb Immobilization Increases IL-1β and Cdkn2a Expression in Skeletal Muscle Fibro-Adipogenic Progenitor Cells: A Link Between Senescence and Muscle Disuse Atrophy
Authors: Parker Emily , Khayrullin Andrew , Kent Andrew , Mendhe Bharati , Youssef El Baradie Khairat Bahgat , Yu Kanglun , Pihkala Jeanene , Liu Yutao , McGee-Lawrence Meghan , Johnson Maribeth , Chen Jie , Hamrick Mark
Published: January 2022

Loss of muscle mass and strength contributes to decreased independence and an increased risk for morbidity and mortality. A better understanding of the cellular and molecular mechanisms underlying muscle atrophy therefore has significant clinical and therapeutic implications. Fibro-adipogenic progenitors (FAPs) are a skeletal muscle resident stem cell population that have recently been shown to play vital roles in muscle regeneration and muscle hypertrophy; however, the role that these cells play in muscle disuse atrophy is not well understood. We investigated the role of FAPs in disuse atrophy in vivo utilizing a 2-week single hindlimb immobilization model. RNA-seq was performed on FAPs isolated from the immobilized and non-immobilized limb. The RNAseq data show that IL-1β is significantly upregulated in FAPs following 2 weeks of immobilization, which we confirmed using droplet-digital PCR (ddPCR). We further validated the RNA-seq and ddPCR data from muscle in situ using RNAscope technology. IL-1β is recognized as a key component of the senescence-associated secretory phenotype, or SASP. We then tested the hypothesis that FAPs from the immobilized limb would show elevated senescence measured by cyclin-dependent kinase inhibitor 2A (Cdkn2a) expression as a senescence marker. The ddPCR and RNAscope data both revealed increased Cdkn2a expression in FAPs with immobilization. These data suggest that the gene expression profile of FAPs is significantly altered with disuse, and that disuse itself may drive senescence in FAPs further contributing to muscle atrophy.
The Establishment of Quantitatively Regulating Expression Cassette with sgRNA Targeting BIRC5 to Elucidate the Synergistic Pathway of Survivin with P-Glycoprotein in Cancer Multi-Drug Resistance
Authors: Deng Changping , Hu Fabiao , Zhao Zhangting , Zhou Yiwen , Liu Yuping , Zhang Tong , Li Shihui , Zheng Wenyun , Zhang Wenliang , Wang Tianwen , Ma Xingyuan
Published: January 2022

Quantitative analysis and regulating gene expression in cancer cells is an innovative method to study key genes in tumors, which conduces to analyze the biological function of the specific gene. In this study, we found the expression levels of Survivin protein (BIRC5) and P-glycoprotein (MDR1) in MCF-7/doxorubicin (DOX) cells (drug-resistant cells) were significantly higher than MCF-7 cells (wild-type cells). In order to explore the specific functions of BIRC5 gene in multi-drug resistance (MDR), a CRISPR/Cas9-mediated knocking-in tetracycline (Tet)-off regulatory system cell line was established, which enabled us to regulate the expression levels of Survivin quantitatively (clone 8 named MCF-7/Survivin was selected for further studies). Subsequently, the determination results of doxycycline-induced DOX efflux in MCF-7/Survivin cells implied that Survivin expression level was opposite to DOX accumulation in the cells. For example, when Survivin expression was down-regulated, DOX accumulation inside the MCF-7/Survivin cells was up-regulated, inducing strong apoptosis of cells (reversal index 118.07) by weakening the release of intracellular drug from MCF-7/Survivin cells. Also, down-regulation of Survivin resulted in reduced phosphorylation of PI3K, Akt, and mTOR in MCF-7/Survivin cells and significantly decreased P-gp expression. Previous studies had shown that PI3K/Akt/mTOR could regulate P-gp expression. Therefore, we speculated that Survivin might affect the expression of P-gp through PI3K/Akt/mTOR pathway. In summary, this quantitative method is not only valuable for studying the gene itself, but also can better analyze the biological phenomena related to it.
A Novel Lactate Metabolism-Related Gene Signature for Predicting Clinical Outcome and Tumor Microenvironment in Hepatocellular Carcinoma
Authors: Li Yue , Mo Huanye , Wu Shengli , Liu Xin , Tu Kangsheng
Published: January 2022

Hepatocellular carcinoma (HCC) is the main subtype of primary liver cancer with high malignancy and poor prognosis. Metabolic reprogramming is a hallmark of cancer and has great importance on the tumor microenvironment (TME). As an abundant metabolite, lactate plays a crucial role in cancer progression and the immunosuppressive TME. Nonetheless, the potential roles of lactate in HCC remain unclear. In this study, we downloaded transcriptomic data of HCC patients with corresponding clinical information from the TCGA and ICGC portals. The TCGA-HCC dataset used as the training cohort, while the ICGC-LIRI-JP dataset was served as an external validation cohort. Cox regression analysis and the LASSO regression model were combined to construct the lactate metabolism-related gene signature (LMRGS). Then, we assessed the clinical significance of LMRGS in HCC. Besides, enriched molecular functions, tumor mutation burden (TMB), infiltrating immune cells, and immune checkpoint were comprehensively analyzed in different LMRGS subgroups. In total, 66 differentially expressed lactate metabolism-related genes (LMRGs) were screened. The functions of LMRGs were mainly enriched in mitochondrial activity and metabolic processes. The LMRGS comprised of six key LMRGs (FKTN, PDSS1, PET117, PUS1, RARS1, and RNASEH1) had significant clinical value for independently predicting the prognosis of HCC patients. The overall survival and median survival of patients in the LMRGS-high group were significantly shorter than in the LMRGS-low group. In addition, there were differences in TMB between the two LMRGS subgroups. The probability of genetic mutations was higher in the LMRGS-high group. Most importantly, the LMRGS reflected the TME characteristics. In the LMRGS-high group, the immune microenvironment presented a suppressed state, accompanied by more inhibitory immune cell infiltration, including follicular helper T cells and regulatory T cells. Additionally, the expression of inhibitory checkpoint molecules was much higher in the LMRGS-high group. Our study suggested that the LMRGS was a robust biomarker to predict the clinical outcomes and evaluate the TME of patients with HCC.
Synthesis of Novel Suramin Analogs With Anti-Proliferative Activity via FGF1 and FGFRD2 Blockade
Authors: Parveen Nuzhat , Lin Yan-Liang , Chou Ruey-Hwang , Sun Chung-Ming , Yu Chin
Published: January 2022

A promising approach in cancer therapy is the inhibition of cell proliferation using small molecules. In this study, we report the synthesis of suramin derivatives and their applications. We used NMR spectroscopy and docking simulations to confirm binding sites and three-dimensional models of the ligand-protein complex. The WST-1 assay was used to assess cell viability and cell proliferation in vitro to evaluate the inhibition of protein–protein interactions and to investigate the anti-proliferative activities in a breast cancer cell line. All the suramin derivatives showed anti-proliferative activity by blocking FGF1 binding to its receptor FGFRD2. The dissociation constant was measured by fluorescence spectroscopy. The suramin compound derivatives synthesized herein show potential as novel therapeutic agents for their anti-proliferative activity via the inhibition of protein–protein interactions. The cytotoxicity of these suramin derivatives was lower than that of the parent suramin compound, which may be considered a significant advancement in this field. Thus, these novel suramin derivatives may be considered superior anti-metastasis molecules than those of suramin.
Development and Validation of a Bioanalytical UHPLC-MS/MS Method Applied to Murine Liver Tissue for the Determination of Indocyanine Green Loaded in H-Ferritin Nanoparticles
Authors: Sottani Cristina , Grignani Elena , Cottica Danilo , Mazzucchelli Serena , Sevieri Marta , Chesi Arianna , Corsi Fabio , Galfrè Sarah , Robustelli della Cuna Francesco Saverio , Calleri Enrica
Published: January 2022

Indocyanine green (ICG) is one of the most commonly used fluorophores in near-infrared fluorescence-guided techniques. However, the molecule is prone to form aggregates in saline solution with a limited photostability and a moderate fluorescence yield. ICG was thus formulated using protein-based nanoparticles of H-ferritin (HFn) in order to generate a new nanostructure, HFn-ICG. In this study, an ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) system was employed to develop and validate the quantitative analysis of ICG in liver tissue samples from HFn-ICG-treated mice. To precipitate HFn, cold acetone in acidic solution at pH 5.0 was used. The processed liver samples were injected into the UHPLC-MS/MS system for analysis using the positive electrospray ionization mode. Chromatographic separation was achieved on a Waters Acquity UPLC® HSS T3 Column (1.8 μm, 2.1 × 100 mm) with 0.1% formic acid and acetonitrile as the mobile phase with gradient elution. The selected reaction monitoring transitions of  m/z 753 →m/z 330 and m/z 827 →m/z 330 were applied for ICG and IR-820 (the internal standard, IS), respectively. The method was selective and linear over a concentration range of 50–1,500 ng/ml. The method was validated for sensitivity, accuracy, precision, extraction recovery, matrix effect, and stability in liver tissue homogenates. ICG extraction recoveries ranged between 85 and 108%. The intra- and inter-day precisions were less than 6.28%. The method was applied to a bio-distribution study to compare the amount of ICG levels from mice treated with HFn-ICG and free ICG. The analyses of the homogenate samples from the two types of treatment showed that the concentration levels of ICG is approximately six-fold higher than those of free ICG (1,411 ± 7.62 ng/ml vs. 235 ± 26.0 ng/ml) at 2 h post injection.
Kinetic Energy Dose as a Unified Metric for Comparing Ball Mills in the Mechanocatalytic Depolymerization of Lignocellulose
Authors: Kessler Martin , Rinaldi Roberto
Published: January 2022

Mechanochemistry utilizes mechanical forces to activate chemical bonds. It offers environmentally benign routes for both (bio) organic and inorganic syntheses. However, direct comparison of mechanochemistry results is often very challenging. In mechanochemical synthetic protocols, ball mill setup (mechanical design and grinding vessel geometry) in addition to experimental parameters (milling frequency, duration, ball count and size) vary broadly. This fact poses a severe issue to further progress in this exciting research area because ball mill setup and experimental parameters govern how much kinetic energy is transferred to a chemical reaction. In this work, we address the challenge of comparing mechanochemical reaction results by taking the energy dose provided by ball mills as a unified metric into account. In this quest, we applied kinematic modeling to two ball mills functioning under distinct working principles to express the energy dose as a mathematical function of the experimental parameters. By examining the effect of energy dose on the extent of the mechanocatalytic depolymerization (MCD) of lignocellulosic biomass (beechwood), we found linear correlations between yield of water-soluble products (WSP) and energy dose for both ball mills. Interestingly, when a substrate layer is formed on the grinding jar wall and/or grinding medium, a weak non-linear correlation between water-soluble products yield and energy dose is identified. We demonstrate that the chemical reaction’s best utilization of kinetic energy is achieved in the linear regime, which presents improved WSP yields for given energy doses. In the broader context, the current analysis outlines the usefulness of the energy dose as a unified metric in mechanochemistry to further the understanding of reaction results obtained from different ball mills operating under varied experimental conditions.
An Integrative Sialomic Analysis Reveals Molecules From Triatoma sordida (Hemiptera: Reduviidae)
Authors: Praça Yanna Reis , Santiago Paula Beatriz , Charneau Sébastien , Mandacaru Samuel Coelho , Bastos Izabela Marques Dourado , Bentes Kaio Luís da Silva , Silva Sofia Marcelino Martins , da Silva Waldeyr Mendes Cordeiro , da Silva Ionizete Garcia , de Sousa Marcelo Valle , Soares Célia Maria de Almeida , Ribeiro José Marcos Chaves , Santana Jaime Martins , de Araújo Carla Nunes
Published: January 2022

Triatomines have evolved salivary glands that produce versatile molecules with various biological functions, including those leading their interactions with vertebrate hosts’ hemostatic and immunological systems. Here, using high-throughput transcriptomics and proteomics, we report the first sialome study on the synanthropic triatomine Triatoma sordida. As a result, 57,645,372 reads were assembled into 26,670 coding sequences (CDS). From these, a total of 16,683 were successfully annotated. The sialotranscriptomic profile shows Lipocalin as the most abundant protein family within putative secreted transcripts. Trialysins and Kazal-type protease inhibitors have high transcript levels followed by ubiquitous protein families and enzyme classes. Interestingly, abundant trialysin and Kazal-type members are highlighted in this triatomine sialotranscriptome. Furthermore, we identified 132 proteins in T. sordida salivary gland soluble extract through LC-MS/MS spectrometry. Lipocalins, Hemiptera specific families, CRISP/Antigen-5 and Kazal-type protein inhibitors proteins were identified. Our study provides a comprehensive description of the transcript and protein compositions of the salivary glands of T. sordida. It significantly enhances the information in the Triatominae sialome databanks reported so far, improving the understanding of the vector’s biology, the hematophagous behaviour, and the Triatominae subfamily’s evolution.
Elevated Expression of lncRNA MEG3 Induces Endothelial Dysfunction on HUVECs of IVF Born Offspring via Epigenetic Regulation
Authors: Jiang Ying , Zhu Hong , Chen Hong , Yu Yi-Chen , Xu Ye-Tao , Liu Fang , He Sai-Nan , Sagnelli Matthew , Zhu Yi-Min , Luo Qiong
Published: January 2022

Cardiovascular dysfunction in children born after in vitro fertilization (IVF) has been of great concern, the potential molecular mechanisms for such long-term outcomes are still unknown. Here, we found that systolic blood pressure was a little higher in IVF born offspring at 2 years old compared to those born after being naturally conceived. Besides, the expression level of maternally expressed gene 3 (MEG3) was higher in human umbilical vein endothelial cells (HUVECs) from IVF offspring than that in spontaneously born offspring. Pearson correlation test showed that MEG3 relative expression is significantly related to the children's blood pressure (Coefficient = 0.429, P = 0.0262). Furthermore, we found decreased expression of endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) along with elevated expression of endothelial-1(ET1) in HUVECs from IVF offspring, accompanied by lower secretion of nitrite, VEGF, and higher secretion of ET1 in the umbilical cord serum of IVF offspring. Correlation analysis showed MEG3 expression highly correlated with ET1 and Nitrate concentration. With pyrosequencing technology, we found that elevated expression of MEG3 was the result of hypomethylation of the MEG3 promoter. Therefore, our results provide a potential mechanism addressing the high-risk of hypertension in IVF offspring via MEG3 epigenetic regulation.
Cardioprotective Effects of n-3 Polyunsaturated Fatty Acids: Orchestration of mRNA Expression, Protein Phosphorylation, and Lipid Metabolism in Pressure Overload Hearts
Authors: Li Xiang , Tan Weijiang , Zheng Shuang , Zhang Junjie , Zhu Caiyi , Cai Chun , Chen Honghua , Yang Chenqi , Kang Le , Pan Zhanhong , Pyle W. Glen , Backx Peter H. , Zou Yunzeng , Yang Feng Hua
Published: January 2022

Background: Pressure overload can result in dilated cardiomyopathy. The beneficial effects of n-3 polyunsaturated fatty acids (n-3 PUFAs) on heart disorders have been widely recognized. However, the molecular mechanisms underlying their protective effects against cardiomyopathy remain unclear.

Methods: Pressure overload in mice induced by 8 weeks of transverse aortic constriction was used to induce dilated cardiomyopathy. A transgenic fat-1 mouse model carrying the n-3 fatty acid desaturase gene fat-1 gene from Caenorhabditis elegans was used to evaluate the mechanism of n-3 PUFAs in this disease. Echocardiography, transmission electron microscopy, and histopathological analyses were used to evaluate the structural integrity and function in pressure overloaded fat-1 hearts. mRNA sequencing, label-free phosphoprotein quantification, lipidomics, Western blotting, RT-qPCR, and ATP detection were performed to examine the effects of n-3 PUFAs in the heart.

Results: Compared with wild-type hearts, left ventricular ejection fraction was significantly improved (C57BL/6J [32%] vs. fat-1 [53%]), while the internal diameters of the left ventricle at systole and diastole were reduced in the fat-1 pressure overload hearts. mRNA expression, protein phosphorylation and lipid metabolism were remodeled by pressure overload in wild-type and fat-1 hearts. Specifically, elevation of endogenous n-3 PUFAs maintained the phosphorylation states of proteins in the subcellular compartments of sarcomeres, cytoplasm, membranes, sarcoplasmic reticulum, and mitochondria. Moreover, transcriptomic analysis predicted that endogenous n-3 PUFAs restored mitochondrial respiratory chain function that was lost in the dilated hearts, and this was supported by reductions in detrimental oxylipins and protection of mitochondrial structure, oxidative phosphorylation, and ATP production.

Conclusions: Endogenous n-3 PUFAs prevents dilated cardiomyopathy via orchestrating gene expression, protein phosphorylation, and lipid metabolism. This is the first study provides mechanistic insights into the cardioprotective effects of n-3 PUFAs in dilated cardiomyopathy through integrated multi-omics data analysis.
The Functional Polymorphism of DDAH2 rs9267551 Is an Independent Determinant of Arterial Stiffness
Authors: Averta Carolina , Mancuso Elettra , Spiga Rosangela , Miceli Sofia , Succurro Elena , Fiorentino Teresa Vanessa , Perticone Maria , Mannino Gaia Chiara , Thamtarana Prapaporn Jungtrakoon , Sciacqua Angela , Sesti Giorgio , Andreozzi Francesco
Published: January 2022

Background: The association of circulating asymmetric dimethylarginine (ADMA) levels with cardiovascular risk and arterial stiffness has been reportedly demonstrated, although the causal involvement of ADMA in the pathogenesis of these conditions is still debated. Dimethylaminohydrolase 2 (DDAH2) is the enzyme responsible for ADMA hydrolysis in the vasculature, and carriers of the polymorphism rs9267551 C in the 5′-UTR of DDAH2 have been reported to have higher DDAH2 expression and reduced levels of serum ADMA.

Approach and Results: We genotyped rs9267551 in 633 adults of European ancestry and measured their carotid–femoral pulse wave velocity (cfPWV), the gold-standard method to estimate arterial stiffness. cfPWV resulted significantly lower in rs9267551 C allele carriers (Δ = −1.12 m/s, P < 0.01) after correction for age, sex and BMI, and a univariate regression showed that the presence of rs9267551 C variant was negatively associated with cfPWV (β = −0.110, P < 0.01). In a multivariable regression model, subjects carrying the rs9267551 C allele manifested significantly lower cfPWV than GG carriers (β = −0.098, P = 0.01) independently from several potential confounders. We measured circulating ADMA levels in a subset of 344 subjects. A mediation analysis revealed that the effect of DDAH2 rs9267551 genotype on cfPWV was mediated by the variation in ADMA levels.

Conclusions: These evidences hint that the presence of rs9267551 C allele may explain, at least in part, a reduction in vessel rigidity as measured by cfPWV, and support the attribution of a causative role to ADMA in the pathogenesis of arterial stiffness.
The Bayes Estimators of the Variance and Scale Parameters of the Normal Model With a Known Mean for the Conjugate and Noninformative Priors Under Stein’s Loss
Authors: Zhang Ying-Ying , Rong Teng-Zhong , Li Man-Man
Published: January 2022

For the normal model with a known mean, the Bayes estimation of the variance parameter under the conjugate prior is studied in Lehmann and Casella (1998) and Mao and Tang (2012). However, they only calculate the Bayes estimator with respect to a conjugate prior under the squared error loss function. Zhang (2017) calculates the Bayes estimator of the variance parameter of the normal model with a known mean with respect to the conjugate prior under Stein’s loss function which penalizes gross overestimation and gross underestimation equally, and the corresponding Posterior Expected Stein’s Loss (PESL). Motivated by their works, we have calculated the Bayes estimators of the variance parameter with respect to the noninformative (Jeffreys’s, reference, and matching) priors under Stein’s loss function, and the corresponding PESLs. Moreover, we have calculated the Bayes estimators of the scale parameter with respect to the conjugate and noninformative priors under Stein’s loss function, and the corresponding PESLs. The quantities (prior, posterior, three posterior expectations, two Bayes estimators, and two PESLs) and expressions of the variance and scale parameters of the model for the conjugate and noninformative priors are summarized in two tables. After that, the numerical simulations are carried out to exemplify the theoretical findings. Finally, we calculate the Bayes estimators and the PESLs of the variance and scale parameters of the S&P 500 monthly simple returns for the conjugate and noninformative priors.
Rare Earth Elements Variations in a Hyperacid Crater Lake and Their Relations With Changes in Phreatic Activity, Physico-Chemical Parameters, and Chemical Composition: The Case of Poás Volcano (Costa Rica)
Authors: Pappaterra Sabrina , Inguaggiato Claudio , Rouwet Dmitri , Mora-Amador Raúl , Ramírez-Umaña Carlos , González Gino , Brusca Lorenzo , Peiffer Loic , Levresse Gilles , Bellomo Sergio
Published: January 2022

Decades of geochemical monitoring at active crater lakes worldwide have confirmed that variations in major elements and physico-chemical parameters are useful to detect changes in volcanic activity. However, it is still arduous to identify precursors of single phreatic eruptions. During the unrest phase of 2009–2016, at least 679 phreatic eruptions occurred at the hyperacid and hypersaline crater lake Laguna Caliente of Poás volcano (Costa Rica). In this study, we investigate the temporal variations of Rare Earth Elements (REE) dissolved in Laguna Caliente in order to 1) scrutinize if they can be used as a new geochemical tool to monitor changes of phreatic activity at hyperacid crater lakes and 2) identify the geochemical processes responsible for the variations of REE concentrations in the lake. The total concentration of REE varies from 950 to 2,773 μg kg−1. (La/Pr)N-local rock ratios range from 0.93 to 1.35, and Light REE over Heavy REE (LREE/HREE)N-local rock ratios vary from 0.71 to 0.95. These same parameters vary in relation to significant changes in phreatic activity; in particular, the (La/Pr)N-local rock ratio increases as phreatic activity increases, while that of (LREE/HREE)N-local rock decreases when phreatic activity increases. REE concentrations and their ratios were compared with the variations of major elements and physico-chemical parameters of the lake. Calcium versus (La/Pr)N-local rock and versus (LREE/HREE)N-local rock ratios show different trends compared to the other major elements (Na, K, Mg, Al, Fe, SO4, and Cl). Moreover, a higher loss of Ca (up to 2,835 ppm) in lake water was found with respect to the loss of Al, K, and Na. This loss of Ca is argued to be due to gypsum precipitation, a process corroborated by the mass balance calculation simulating the precipitation of gypsum and the contemporaneous removal of REE from the lake water. The observed relations between REE, changes in phreatic activity, and the parameters commonly used for the monitoring of hyperacid volcanic lakes encourage investigating more on the temporal and cause-effect relationship between REE dynamics and changes in phreatic activity at crater lake-bearing volcanoes.
Learning About Viruses: Representing Covid-19
Authors: Manches Andrew , Ainsworth Shaaron
Published: January 2022

Covid-19 has significantly impacted children’s lives, requiring them to process multiple messages with significant emotional, social, and behavioural implications. Yet, the vast majority of these messages solely focus on behaviour. This is an oversight as children and young people can understand the biological properties and mechanisms of viruses when supported appropriately, thereby presenting an important opportunity for educators. However, like many other invisible scientific phenomena, understanding of viruses greatly depends upon how they are represented. Thus, we sought to understand the relative benefits and limitations of different forms for learning about the underlying biology of Covid-19. Applying an embodied learning lens, we analysed pictures, 3d models, gestures, dynamic visualisations, interactive representations, and extended reality identified through a state-of-the art-review. In so doing, we address the affordances and limitations of these forms in general and variation within them. We used this to develop a representational checklist that teachers and other adults can use to help them support children and young people’s learning about the biology of Covid-19.
Tertiary Control for Energy Management of EV Charging Station Integrated With PV and Energy Storage
Authors: Dan Yangqing , Liu Shuran , Zhu Yanwei , Xie Hailian
Published: January 2022

Along with the rapid increase in the number of electric vehicles, more and more EV charging stations tend to have charging infrastructure, rooftop photovoltaic and energy storage all together for energy saving and emission reduction. Compared with individual design for each of the components in such kind of systems, an integrated design can result in higher efficiency, increased reliability, and lower total capital cost. This paper mainly focuses on the tertiary control strategy for dynamic state operation, such as PV generation fluctuation and random arrival/leave of EVs. The tertiary control aims to achieve stable operation under dynamic states, as well as to optimize the energy flow in the station to realize maximal operational benefits with constraints such as peak/valley price of electricity, state of discharge limitation of battery, etc. In this paper, four energy management functions in tertiary control level are proposed, and their performance is verified by simulations. By using prediction of PV power and EV load in the following 72 h, a novel tertiary control logic is proposed to optimize PVC and ESC power flow by changing their droop characteristics, so that minimum operational cost for the station can be achieved. Furthermore, a sensitivity analysis is conducted for three parameters, including ES battery capacity, weather influence, and PV and EV load prediction error. The results from sensitivity analysis indicate that ES battery capacity and weather condition lead to a great impact on the operational cost of the integrated charging station, while a typical prediction error of PV power and EV load will not influence the optimization result significantly.
Side Tributary Distribution of Quasi-Uniform Iterative Binary Tree Networks for River Networks
Authors: Wang Keyi , Zhang Li , Li Tiejian , Li Xiang , Guo Biyun , Chen Guoxin , Huang Yuefei , Wei Jiahua
Published: January 2022

Self-similarity and plane-filling are intrinsic structure properties of natural river networks. Statistical data indicates that most natural river networks are Tokunaga trees. Researchers have explored to use iterative binary tree networks (IBTNs) to simulate natural river networks. However, the characteristics of natural rivers such as Tokunaga self-similarity and plane-filling cannot be easily guaranteed by the configuration of the IBTN. In this paper, the generator series and a quasi-uniform iteration rule are specified for the generation of nonstochastic quasi-uniform iterative binary tree networks (QU-IBTNs). First, we demonstrate that QU-IBTNs definitely satisfy self-similarity. Second, we show that the constraint for a QU-IBTN to be a Tokunaga tree is that the exterior links must be replaced in the generator series with a neighboring generator that is larger than the interior links during the iterative process. Moreover, two natural river networks are examined to reveal the inherent consistency with QU-IBTN at low Horton-Strahler orders.
Brazilian Mangroves: Blue Carbon Hotspots of National and Global Relevance to Natural Climate Solutions
Authors: Rovai Andre S. , Twilley Robert R. , Worthington Thomas A. , Riul Pablo
Published: January 2022

Mangroves are known for large carbon stocks and high sequestration rates in biomass and soils, making these intertidal wetlands a cost-effective strategy for some nations to compensate for a portion of their carbon dioxide (CO2) emissions. However, few countries have the national-level inventories required to support the inclusion of mangroves into national carbon credit markets. This is the case for Brazil, home of the second largest mangrove area in the world but lacking an integrated mangrove carbon inventory that captures the diversity of coastline types and climatic zones in which mangroves are present. Here we reviewed published datasets to derive the first integrated assessment of carbon stocks, carbon sequestration rates and potential CO2eq emissions across Brazilian mangroves. We found that Brazilian mangroves hold 8.5% of the global mangrove carbon stocks (biomass and soils combined). When compared to other Brazilian vegetated biomes, mangroves store up to 4.3 times more carbon in the top meter of soil and are second in biomass carbon stocks only to the Amazon forest. Moreover, organic carbon sequestration rates in Brazilian mangroves soils are 15–30% higher than recent global estimates; and integrated over the country’s area, they account for 13.5% of the carbon buried in world’s mangroves annually. Carbon sequestration in Brazilian mangroves woody biomass is 10% of carbon accumulation in mangrove woody biomass globally. Our study identifies Brazilian mangroves as a major global blue carbon hotspot and suggest that their loss could potentially release substantial amounts of CO2. This research provides a robust baseline for the consideration of mangroves into strategies to meet Brazil’s intended Nationally Determined Contributions.
Identification of Five Cytotoxicity-Related Genes Involved in the Progression of Triple-Negative Breast Cancer
Authors: Zhang Yan , Tong Gui-hui , Wei Xu-Xuan , Chen Hai-yang , Liang Tian , Tang Hong-Ping , Wu Chuan-An , Wen Guo-Ming , Yang Wei-Kang , Liang Li , Shen Hong
Published: January 2022

Background: Breast cancer is one of the deadly tumors in women, and its incidence continues to increase. This study aimed to identify novel therapeutic molecules using RNA sequencing (RNA-seq) data of breast cancer from our hospital.

Methods: 30 pairs of human breast cancer tissue and matched normal tissue were collected and RNA sequenced in our hospital. Differentially expressed genes (DEGs) were calculated with raw data by the R package “edgeR”, and functionally annotated using R package “clusterProfiler”. Tumor-infiltrating immune cells (TIICs) were estimated using a website tool TIMER 2.0. Effects of key genes on therapeutic efficacy were analyzed using RNA-seq data and drug sensitivity data from two databases: the Cancer Cell Line Encyclopedia (CCLE) and the Cancer Therapeutics Response Portal (CTRP).

Results: There were 2,953 DEGs between cancerous and matched normal tissue, as well as 975 DEGs between primary breast cancer and metastatic breast cancer. These genes were primarily enriched in PI3K-Akt signaling pathway, calcium signaling pathway, cAMP signaling pathway, and cell cycle. Notably, CD8+ T cell, M0 macrophage, M1 macrophage, regulatory T cell and follicular helper T cell were significantly elevated in cancerous tissue as compared with matched normal tissue. Eventually, we found five genes (GALNTL5, MLIP, HMCN2, LRRN4CL, and DUOX2) were markedly corelated with CD8+ T cell infiltration and cytotoxicity, and associated with therapeutic response.

Conclusion: We found five key genes associated with tumor progression, CD8+ T cell and therapeutic efficacy. The findings would provide potential molecular targets for the treatment of breast cancer.
Identification and Verification of Five Potential Biomarkers Related to Skin and Thermal Injury Using Weighted Gene Co-Expression Network Analysis
Authors: Yang Ronghua , Wang Zhengguang , Li Jiehua , Pi Xiaobing , Wang Xiaoxiang , Xu Yang , Shi Yan , Zhou Sitong
Published: January 2022

Background: Burn injury is a life-threatening disease that does not have ideal biomarkers. Therefore, this study first applied weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) screening methods to identify pivotal genes and diagnostic biomarkers associated with the skin burn process.

Methods: After obtaining transcriptomic datasets of burn patient skin and normal skin from Gene Expression Omnibus (GEO) and performing differential analysis and functional enrichment, WGCNA was used to identify hub gene modules associated with burn skin processes in the burn patient peripheral blood sample dataset and determine the correlation between modules and clinical features. Enrichment analysis was performed to identify the functions and pathways of key module genes. Differential analysis, WGCNA, protein-protein interaction analysis, and enrichment analysis were utilized to screen for hub genes. Hub genes were validated in two other GEO datasets, tested by immunohistochemistry for hub gene expression in burn patients, and receiver operating characteristic curve analysis was performed. Finally, we constructed the specific drug activity, transcription factors, and microRNA regulatory network of the five hub genes.

Results: A total of 1,373 DEGs in GSE8056 were obtained, and the top 5 upregulated genes were S100A12, CXCL8, CXCL5, MMP3, and MMP1, whereas the top 5 downregulated genes were SCGB1D2, SCGB2A2, DCD, TSPAN8, and KRT25. DEGs were significantly enriched in the immunity, epidermal development, and skin development processes. In WGCNA, the yellow module was identified as the most closely associated module with tissue damage during the burn process, and the five hub genes (ANXA3, MCEMP1, MMP9, S100A12, and TCN1) were identified as the key genes for burn injury status, which consistently showed high expression in burn patient blood samples in the GSE37069 and GSE13902 datasets. Furthermore, we verified using immunohistochemistry that these five novel hub genes were also significantly elevated in burn patient skin. In addition, MCEMP1, MMP9, and S100A12 showed perfect diagnostic performance in the receiver operating characteristic analysis.

Conclusion: In conclusion, we analyzed the changes in genetic processes in the skin during burns and used them to identify five potential novel diagnostic markers in blood samples from burn patients, which are important for burn patient diagnosis. In particular, MCEMP1, MMP9, and S100A12 are three key blood biomarkers that can be used to identify skin damage in burn patients.
Low Detection Rates of Genetic FH in Cohort of Patients With Severe Hypercholesterolemia in the United Arabic Emirates
Authors: Rimbert Antoine , Daggag Hinda , Lansberg Peter , Buckley Adam , Viel Martijn , Kanninga Roan , Johansson Lennart , Dullaart Robin P. F. , Sinke Richard , Al Tikriti Alia , Kuivenhoven Jan Albert , Barakat Maha Taysir
Published: January 2022

Background: Programs to screen for Familial hypercholesterolemia (FH) are conducted worldwide. In Western societies, these programs have been shown to be cost-effective with hit/detection rates of 1 in 217–250. Thus far, there is no published data on genetic FH in the Gulf region. Using United Arab Emirates as a proxy for the Gulf region, we assessed the prevalence of genetically confirmed FH in the Emirati population sample.

Materials and Methods: We recruited 229 patients with LDL-C >95th percentile and employed a customized next generation sequencing pipeline to screen canonical FH genes (LDLR, APOB, PCSK9, LDLRAP1).

Results: Participants were characterized by mean total cholesterol and low-density lipoprotein cholesterol (LDL-c) of 6.3 ± 1.1 and 4.7 ± 1.1 mmol/L respectively. Ninety-six percent of the participants were using lipid-lowering medication with mean corrected LDL-c values of 10.0 ± 3.0 mmol/L 15 out of 229 participants were found to suffer from genetically confirmed FH. Carriers of causal genetic variants for FH had higher on-treatment LDL-c compared to those without causal variants (5.7 ± 1.5 vs 4.7 ± 1.0; p = 3.7E-04). The groups did not differ regarding high-density lipoprotein cholesterol, triglycerides, body mass index, blood pressure, glucose, and glycated haemoglobin.

Conclusion: This study reveals a low 7% prevalence of genetic FH in Emiratis with marked hypercholesterolemia as determined by correcting LDL-c for the use of lipid-lowering treatment. The portfolio of mutations identified is, to a large extent, unique and includes gene duplications. Our findings warrant further studies into origins of hypercholesterolemia in these patients. This is further supported by the fact that these patients are also characterized by high prevalence of type 2 diabetes (42% in the current study cohort) which already puts them at an increased risk of atherosclerotic cardiovascular disease. These results may also be useful in public health initiatives for FH cascade screening programs in the UAE and maybe the Gulf region.
A Systematic Review and Meta-Analysis on Multiple Cytokine Gene Polymorphisms in the Pathogenesis of Periodontitis
Authors: Liu Xin , Li Hui
Published: January 2022

Aim

Periodontitis is an inflammatory disease that destroys both soft and hard periodontal tissues. However, a complex periodontal cytokine network remains unclear. This systematic review explored multiple cytokine gene polymorphisms in the pathogenesis of periodontitis.

Material and Methods

A systematic search was performed using the databases from previous publications, which indicated the association between cytokine polymorphisms and periodontitis pathogenesis. Meta-analysis was conducted using fixed or randomized models to calculate the significance of multiple cytokine polymorphisms. A total of 147 articles were analyzed with polymorphisms in 12 interleukins [Th1 (IL-2, IFN-γ, and TNF-α), Th2 (IL-4 and IL-13), Th17 (IL-1α, IL-1β, IL-6, and IL-17), and Treg cytokines (IL-10 and TGF-β)]. Doi plot was used to probe the occurrence of publication bias.

Results

The polymorphisms of IL-2 and TNF-α of Th1 cytokine family may be associated with the pathogenesis or the prevention of periodontitis risk, while the polymorphism of IFN-γ is not related to periodontitis risk. The polymorphisms for IL-4 and IL-13 of Th2 cytokine family are not found to be associated with the pathogenesis of periodontitis. For the polymorphisms of the members of Th17 cytokine family, different IL-1α polymorphisms may have inverse actions in the pathogenesis of periodontitis. IL-1β is a noteworthy cytokine biomarker in periodontitis development and progression. IL-6 may have a protective function in the inflammatory responses of periodontitis, and IL-17 has a weak relationship the inflammatory responses. The polymorphisms for the members of Treg cell cytokines may have a protective function against periodontitis risk. LFK indexes show the major asymmetry due to publication bias.

Conclusion

IL-1β is a notable cytokine biomarker in periodontitis risk. Treg cytokines favor an anti-inflammatory and protective environment. Further data are needed to confirm the present conclusion due to publication bias.
Autoinflammatory Keratinization Disease With Hepatitis and Autism Reveals Roles for JAK1 Kinase Hyperactivity in Autoinflammation
Authors: Takeichi Takuya , Lee John Y. W. , Okuno Yusuke , Miyasaka Yuki , Murase Yuya , Yoshikawa Takenori , Tanahashi Kana , Nishida Emi , Okamoto Tatsuya , Ito Komei , Muro Yoshinao , Sugiura Kazumitsu , Ohno Tamio , McGrath John A. , Akiyama Masashi
Published: January 2022

Heterozygous mutations in JAK1 which result in JAK-STAT hyperactivity have been implicated in an autosomal dominant disorder that features multi-organ immune dysregulation. This study identifies another previously unreported heterozygous missense JAK1 mutation, H596D, in an individual with a unique autoinflammatory keratinization disease associated with early-onset liver dysfunction and autism. Using CRISPR-Cas9 gene targeting, we generated mice with an identical Jak1 knock-in missense mutation (Jak1H595D/+;I596I/+;Y597Y/+ mice) that recapitulated key aspects of the human phenotype. RNA sequencing of samples isolated from the Jak1H595D/+;I596I/+;Y597Y/+ mice revealed the upregulation of genes associated with the hyperactivation of tyrosine kinases and NF-κB signaling. Interestingly, there was a strong correlation between genes downregulated in Jak1H595D/+;I596I/+;Y597Y/+ mice and those downregulated in the brain of model mice with 22q11.2 deletion syndrome that showed cognitive and behavioral deficits, such as autism spectrum disorders. Our findings expand the phenotypic spectrum of JAK1-associated disease and underscore how JAK1 dysfunction contributes to this autoinflammatory disorder.
Comprehensive Analysis of Expression, Prognostic Value, and Immune Infiltration for Ubiquitination-Related FBXOs in Pancreatic Ductal Adenocarcinoma
Authors: Zhang Yalu , Liu Qiaofei , Cui Ming , Wang Mengyi , Hua Surong , Gao Junyi , Liao Quan
Published: January 2022

Pancreatic ductal adenocarcinoma (PDAC) is one of the most refractory human malignancies. F-box only proteins (FBXO) are the core components of SKP1-cullin 1-F-box E3 ubiquitin ligase, which have been reported to play crucial roles in tumor initiation and progression via ubiquitination-mediated proteasomal degradation. However, the clinical implications and biological functions of FBXOs in PDAC have not been fully clarified. Herein we perform a comprehensive analysis for the clinical values and functional roles of FBXOs in PDAC using different public databases. We found that FBXO1 (CCNF), FBXO20 (LMO7), FBXO22, FBXO28, FBXO32, and FBXO45 (designated six-FBXOs) were robustly upregulated in PDAC tissues, which predicted an adverse prognosis of PDAC patients. There was a significant correlation between the expression levels of six-FBXOs and the clinicopathological features in PDAC. The transcriptional levels of six-FBXOs were subjected to the influence of promoter methylation levels. There were more than 40% genetic alterations and mutations of six-FBXOs, which affected the clinical outcome of PDAC patients. Furthermore, the expression of six-FBXOs was associated with immune infiltrations and activated status, including B cells, CD8+ T cells, CD4+ T cells, NK cells, macrophages, and dendritic cells. The functional prediction revealed that the six-FBXOs were involved in ubiquitination-related pathways and other vital signaling pathways, such as p53, PI3K/Akt, and Hippo pathway. Therefore, six-FBXOs are the promising prognostic biomarkers or potential targets for PDAC diagnosis and treatment.